Infectious Disease and Microbiology – Methylobacterium Species

Overview

Methylobacterium species are aerobic Gram-negative bacilli that are widely distributed in the environment but are very rare causes of human infection. They are distinctive because many species produce characteristic pink-pigmented colonies in culture.

Human disease is usually opportunistic and occurs particularly in immunocompromised patients or in association with indwelling medical devices. Important manifestations include bacteremia and peritoneal dialysis-associated peritonitis.

Classification

Genus: Methylobacterium

Important species:

• M. extorquens

• M. mesophilicum

• Other Methylobacterium species

Type: Aerobic Gram-negative bacillus

Historical Classification

Methylobacterium species were previously classified under the genus:

Protomonas

Therefore, older microbiology literature may refer to these organisms as:

Protomonas species

Microbiologic Characteristics

Methylobacterium organisms are:

• Aerobic

• Gram-negative bacilli

• Environmental organisms

• Generally slow-growing

• Characteristically associated with pink-pigmented colonies

The pink coloration is an important laboratory clue.

Pink-Pigmented Colonies

A particularly characteristic feature of Methylobacterium is the production of:

Pink to reddish-pink colonies

For this reason, these organisms are sometimes described as:

Pink-pigmented facultative methylotrophs

The unusual pigmentation can help distinguish them from many other nonfermenting environmental Gram-negative bacilli.

Incubation Period

The incubation period is:

Unknown

Because infections are usually opportunistic and often associated with medical devices or environmental exposure, a clearly defined incubation period is generally unavailable.

Epidemiology

Human infection is:

Very rare

However, recognition of Methylobacterium infections has increased with improved microbiologic identification techniques and greater awareness of opportunistic environmental organisms.

Environmental Reservoir

Methylobacterium species are widely distributed in:

• Water

• Soil

• Plants

• Moist environmental surfaces

Their ability to persist in water-associated environments is particularly relevant to healthcare-associated infection.

Risk Factors

Invasive infection occurs primarily in patients with:

• Immunosuppression

• Malignancy

• Indwelling vascular catheters

• Peritoneal dialysis catheters

• Other implanted medical devices

Thus, isolation of Methylobacterium from a normally sterile specimen in a vulnerable patient should not automatically be dismissed as contamination.

Bacteremia

One of the most important clinical manifestations is:

Bacteremia

This is particularly associated with immunocompromised individuals and patients with intravascular devices.

Catheter-Associated Infection

Because Methylobacterium is an environmental organism with an affinity for moist environments, infection can occur in association with:

Central venous catheters

Persistent bacteremia may indicate colonization or infection of an indwelling device.

High-Yield Bacteremia Pattern

Immunocompromised patient

• ●

Indwelling vascular catheter

• ●

Gram-negative bacillus

• ●

Pink-pigmented colonies

→ Think Methylobacterium

Peritoneal Dialysis-Associated Peritonitis

Methylobacterium species may cause:

Peritonitis

in patients undergoing:

Peritoneal dialysis

The dialysis catheter provides a potential route for introduction and persistence of the organism.

Clinical Features

Peritoneal dialysis-associated infection may present with:

• Abdominal pain

• Fever

• Cloudy dialysis fluid

• Peritoneal inflammatory findings

Culture of the peritoneal dialysis fluid can establish the microbiologic diagnosis.

Opportunistic Infection

Methylobacterium is considered a:

Low-virulence opportunistic pathogen

Most clinically significant infections occur when normal host defenses are impaired or when foreign material provides a surface for persistent infection.

Colonization vs. True Infection

Because Methylobacterium is an environmental organism, a positive culture should be interpreted according to the clinical setting.

Evidence supporting true infection includes:

• Repeated positive cultures

• Isolation from a normally sterile site

• Compatible clinical illness

• Immunosuppression

• Presence of an infected catheter or device

Diagnosis

The primary diagnostic method is:

Culture

Identification is based on growth characteristics and microbiologic testing.

Laboratory Clue

A particularly useful clue is:

Pink-pigmented colonies

When an unusual aerobic Gram-negative bacillus with pink pigmentation is recovered from blood or another sterile specimen, Methylobacterium should be considered.

Modern Identification

Because unusual environmental Gram-negative bacilli can be difficult to distinguish using conventional biochemical methods, specialized identification techniques may be helpful.

These can include:

• MALDI-TOF mass spectrometry

• Molecular identification methods

Accurate species identification may be important when determining clinical significance and antimicrobial susceptibility.

Treatment

The source lists:

Trimethoprim–sulfamethoxazole (TMP-SMX)

as treatment.

Because Methylobacterium infections are uncommon and susceptibility patterns can vary, treatment should ideally be guided by:

Antimicrobial susceptibility testing

Source Control

For infections associated with:

Central venous catheters

or

Peritoneal dialysis catheters

management may require consideration of:

Catheter removal

in addition to antimicrobial therapy, particularly when infection persists.

Treatment Principle

Clinically significant Methylobacterium infection

↓

Obtain cultures and susceptibility testing

↓

Administer an active antimicrobial

• ●

Evaluate infected catheter/device

↓

Remove or replace device when necessary

Prevention

Because these organisms are environmental and associated with water and moist surfaces, prevention in healthcare settings depends on:

• Appropriate catheter care

• Aseptic technique

• Proper handling of dialysis equipment

• Prevention of contamination of medical fluids and devices

• Appropriate infection-control practices

Methylobacterium vs. Pseudomonas

Methylobacterium

→ Aerobic Gram-negative bacillus

→ Environmental organism

→ Pink-pigmented colonies

→ Rare opportunistic infection

→ Catheter-associated bacteremia and peritonitis

Pseudomonas aeruginosa

→ Aerobic Gram-negative bacillus

→ Common opportunistic pathogen

→ Blue-green pigments may occur

→ Pneumonia, bacteremia, UTI, wound infection, and device-associated infection

The distinctive pink pigmentation is an important clue favoring Methylobacterium.

High-Yield Clinical Pattern

Immunocompromised patient

• ●

Central venous or peritoneal dialysis catheter

• ●

Bacteremia or peritonitis

• ●

Pink-pigmented aerobic Gram-negative bacillus

→ Think Methylobacterium species

Exam Essentials

Genus: Methylobacterium

Important species: M. extorquens, M. mesophilicum

Older name: Protomonas species

Type: Aerobic Gram-negative bacillus

Characteristic culture finding: Pink-pigmented colonies

Distribution: Environmental; associated with soil, plants, and water

Frequency of human infection: Very rare

Major risk group: Immunocompromised patients

Important device association: Vascular and peritoneal dialysis catheters

Major infections: Bacteremia and peritonitis

Diagnosis: Culture

Source treatment: Trimethoprim–sulfamethoxazole

ADDITIONAL TREATMENT • Ciprofloxacin • Aminoglycoside

Treatment principle: Susceptibility-guided antimicrobial therapy plus appropriate device/source control

Key clinical pearl: Methylobacterium is a rare opportunistic aerobic Gram-negative bacillus distinguished by its characteristic pink-pigmented colonies. Think of it when an immunocompromised patient with an indwelling catheter develops otherwise unexplained bacteremia or peritoneal dialysis-associated peritonitis.

Infectious Disease and Microbiology – Metagonimus yokogawai

Overview

Metagonimus yokogawai is a small intestinal trematode (fluke) that causes metagonimiasis. Human infection is usually asymptomatic, although heavier infections may produce gastrointestinal symptoms such as diarrhea, abdominal discomfort, and dyspepsia.

Humans typically acquire infection by eating raw or inadequately cooked freshwater fish containing infective metacercariae.

Classification

Genus: Metagonimus

Species: Metagonimus yokogawai

Type: Trematode helminth

Disease: Metagonimiasis

Major site of infection: Small intestine

Microbiologic Characteristics

M. yokogawai is a foodborne intestinal fluke.

The adult worms are small and inhabit the:

Small intestine

Like other trematodes, the parasite has a complex life cycle involving intermediate hosts before reaching humans.

Life Cycle

The general life cycle is:

Eggs passed in human or animal feces

↓

Development in a freshwater snail

↓

Cercariae released from the snail

↓

Cercariae penetrate freshwater fish

↓

Development into metacercariae in fish tissues

↓

Human eats raw or undercooked infected fish

↓

Metacercariae develop into adult worms in the small intestine

↓

Eggs are passed in feces

Transmission

Human infection occurs primarily through consumption of:

Raw, undercooked, or inadequately processed freshwater fish

containing:

Metacercariae

Thus, metagonimiasis is primarily a foodborne trematode infection.

Incubation Period

The incubation period is:

Not clearly established

Symptoms, when present, generally develop after the parasites mature within the intestine.

Epidemiology

Symptomatic human infection is relatively:

Rare

Cases have been reported from several regions, particularly in areas where raw or inadequately cooked freshwater fish is traditionally consumed.

Reported regions include:

• Russia

• Middle East

• India

• Indonesia

• Philippines

• China

• Japan

• Taiwan

East Asia represents an especially important endemic region for intestinal fluke infections.

Clinical Infection

The disease caused by M. yokogawai is:

Metagonimiasis

Most infections are:

Asymptomatic

Clinical severity generally increases with the number of worms present.

Gastrointestinal Manifestations

Symptomatic infection may produce:

• Diarrhea

• Abdominal discomfort

• Abdominal pain

• Dyspepsia

• Nausea

Heavy worm burdens may cause greater intestinal irritation and inflammation.

Pathogenesis

The characteristic sequence is:

Consumption of raw/undercooked infected freshwater fish

↓

Ingestion of metacercariae

↓

Development of adult flukes in small intestine

↓

Intestinal mucosal irritation

↓

Diarrhea and abdominal symptoms

Diagnosis

Diagnosis is primarily made through:

Microscopic examination of stool specimens

The characteristic finding is:

Trematode eggs in the stool

Repeated or concentrated stool examinations may improve detection when parasite burden is low.

Diagnostic Challenge

The eggs of M. yokogawai are small and can resemble those of other intestinal or hepatobiliary flukes, particularly:

Heterophyes heterophyes

Therefore, identification based solely on egg morphology may sometimes be difficult.

Treatment

The treatment described in the source is:

Praziquantel 25 mg/kg orally every 8 hours for 1 day

This provides:

3 total doses

Praziquantel is highly effective against intestinal trematode infections such as metagonimiasis.

Prevention

Prevention primarily involves:

• Thoroughly cooking freshwater fish

• Avoiding raw or inadequately cooked fish in endemic areas

• Appropriate food preparation

• Proper sanitation to reduce contamination of freshwater environments with parasite eggs

Metagonimus vs. Heterophyes

Metagonimus yokogawai

→ Small intestinal trematode

→ Raw/undercooked freshwater fish

→ Usually asymptomatic

→ Diarrhea and abdominal discomfort when symptomatic

→ Eggs detected in stool

Heterophyes heterophyes

→ Minute intestinal trematode

→ Raw, undercooked, or inadequately salted fish

→ Usually asymptomatic

→ May cause diarrhea and abdominal discomfort

→ Eggs detected in stool

The two infections can be difficult to distinguish solely by stool egg morphology.

Metagonimus vs. Clonorchis

Metagonimus yokogawai

→ Raw freshwater fish

→ Adult worms in small intestine

→ Primarily gastrointestinal symptoms

Clonorchis sinensis

→ Raw freshwater fish

→ Adult worms in biliary tract

→ Cholangitis and biliary obstruction

→ Chronic infection increases risk of cholangiocarcinoma

Thus, the exposure can be similar, but the major anatomic location differs.

High-Yield Clinical Pattern

Consumption of raw or undercooked freshwater fish

• ●

East Asian or other endemic-region exposure

• ●

Diarrhea and abdominal discomfort

• ●

Small trematode eggs in stool

→ Think Metagonimus yokogawai

→ Metagonimiasis

Exam Essentials

Organism: Metagonimus yokogawai

Type: Trematode helminth

Disease: Metagonimiasis

Major location: Small intestine

Distribution: Particularly associated with parts of Asia, with cases reported elsewhere

Transmission: Eating raw or undercooked infected freshwater fish

Infective stage for humans: Metacercariae

First intermediate host: Freshwater snail

Second intermediate host: Freshwater fish

Most infections: Asymptomatic

Major symptoms: Diarrhea, abdominal discomfort, dyspepsia

Diagnosis: Microscopic stool examination for eggs

Treatment: Praziquantel 25 mg/kg orally every 8 hours for 1 day (3 doses)

Prevention: Thoroughly cook freshwater fish

Key clinical pearl: Metagonimus yokogawai is a small intestinal fluke acquired from raw or undercooked freshwater fish. Most infections are asymptomatic, but heavier infections produce diarrhea and abdominal discomfort; diagnosis is made by detecting eggs in stool, and praziquantel is the treatment of choice.

Infectious Disease and Microbiology – Mansonella Species

Overview

Mansonella species are filarial nematodes that cause human infections collectively known as mansonellosis. Important human species include Mansonella ozzardi, M. perstans, and M. streptocerca.

Compared with several other filarial infections, Mansonella infections are generally milder and frequently asymptomatic. When symptoms occur, manifestations may include pruritus, dermatitis, hypopigmented skin lesions, edema, arthralgia, and nonspecific systemic symptoms.

Classification

Genus: Mansonella

Species:

• M. ozzardi

• M. perstans

• M. streptocerca

Type: Filarial nematode

Disease: Mansonellosis

Microbiologic Characteristics

Mansonella species are tissue-dwelling filarial nematodes.

Their life cycle involves:

Adult worms

↓

Production of microfilariae

↓

Microfilariae present in blood or skin, depending on species

↓

Uptake by an arthropod vector

↓

Development of infective larvae

↓

Transmission to another human during a subsequent bite

Incubation Period

The incubation period is:

Not clearly established

Because these infections may remain asymptomatic for prolonged periods, the interval between infection and recognizable disease can be difficult to determine.

Transmission

Mansonella species are transmitted by small biting insects.

Important vectors include:

Biting midges (Culicoides)

and, for some transmission cycles:

Blackflies (Simulium)

The specific vector differs according to the Mansonella species and geographic region.

Mansonella ozzardi

Epidemiology

M. ozzardi occurs primarily in:

• Central America

• South America

• West Indies/Caribbean

It is therefore predominantly a parasite of the:

New World

Clinical Manifestations

Many M. ozzardi infections are asymptomatic.

Symptomatic patients may develop:

• Fever

• Headache

• Pruritus

• Arthralgia

• Lymphadenopathy

• Eosinophilia

• Nonspecific skin manifestations

Microfilariae

The microfilariae of M. ozzardi circulate primarily in:

Peripheral blood

This makes examination of blood an important diagnostic approach.

Mansonella perstans

Epidemiology

M. perstans occurs predominantly in:

West and Central Africa

and has also historically been reported in parts of:

South America

Its true geographic distribution may be broader than recognized because many infections are asymptomatic or minimally symptomatic.

Clinical Manifestations

M. perstans infection is often asymptomatic but may produce:

• Pruritus

• Angioedema

• Fever

• Headache

• Arthralgia

• Abdominal discomfort

• Eosinophilia

Adult worms characteristically inhabit:

Serous body cavities and connective tissues

Microfilariae

M. perstans microfilariae circulate in:

Peripheral blood

Unlike Loa loa, their detection is not characterized by the same classic daytime periodicity.

Mansonella streptocerca

Epidemiology

M. streptocerca occurs predominantly in:

West and Central Africa

Clinical Manifestations

This species is particularly associated with:

Cutaneous disease

Possible manifestations include:

• Pruritic dermatitis

• Hypopigmented lesions

• Papular skin lesions

• Skin thickening

Because of its cutaneous manifestations, infection may resemble:

Onchocerca volvulus infection

Microfilariae

Unlike M. ozzardi and M. perstans, the microfilariae of M. streptocerca are primarily found in:

Skin

This distinction is especially important diagnostically.

Species Comparison

M. ozzardi

→ Central/South America and Caribbean

→ Microfilariae mainly in blood

M. perstans

→ Primarily Africa

→ Adult worms associated with body cavities

→ Microfilariae in blood

M. streptocerca

→ West/Central Africa

→ Cutaneous disease

→ Microfilariae primarily in skin

Clinical Infection

Overall, mansonellosis is generally considered:

Milder than many other filarial infections

A substantial proportion of infected individuals remain:

Asymptomatic

Dermatologic Disease

The source particularly emphasizes:

Hypopigmented pruritic dermatitis

This is especially relevant to M. streptocerca infection.

Patients may experience:

• Itching

• Hypopigmentation

• Papular eruptions

• Chronic localized dermatitis

Diagnosis

Diagnosis depends on the infecting species and may involve:

• Examination for microfilariae

• Skin biopsy or skin snip

• Peripheral blood examination

• Histopathology

• Serology

Blood Examination

For:

M. ozzardi

and

M. perstans

microfilariae can be detected in:

Peripheral blood

Microscopic examination of appropriately prepared blood specimens may establish the diagnosis.

Skin Examination

For:

M. streptocerca

microfilariae are primarily detected in:

Skin specimens

Histopathologic examination or examination of skin tissue can therefore be useful.

Serology

The source also lists:

Serologic testing

However, serologic assays may demonstrate cross-reactivity with other filarial infections and may not always identify the exact Mansonella species.

Treatment

The source describes a historical regimen of:

Diethylcarbamazine (DEC)

with:

50 mg on day 1

↓

100 mg on days 2 and 3

↓

50 mg every 8 hours for 3 weeks

Treatment response varies substantially among Mansonella species, so therapy should be considered species-specific rather than assuming that one regimen is equally effective for all mansonellosis.

Additional Treatment

The source identifies a possible role for:

Doxycycline

Doxycycline can be useful against filarial parasites that depend on intracellular bacterial endosymbionts called:

Wolbachia

Reduction of Wolbachia can impair the survival and reproduction of susceptible filarial worms.

Its usefulness varies among Mansonella species.

Prevention

Prevention primarily involves reducing exposure to biting insect vectors.

Measures include:

• Protective clothing

• Insect repellents

• Screening or other barriers when appropriate

• Avoiding heavy exposure to biting midges and blackflies in endemic areas

Mansonella vs. Loa loa

Mansonella

→ Biting midges/blackflies

→ Usually mild or asymptomatic

→ Blood or skin microfilariae depending on species

→ M. streptocerca causes pruritic dermatitis

Loa loa

→ Chrysops deer fly

→ Calabar swellings

→ Subconjunctival “eye worm”

→ Diurnally periodic blood microfilariae

Mansonella streptocerca vs. Onchocerca volvulus

M. streptocerca

→ Microfilariae in skin

→ Pruritic/hypopigmented dermatitis

→ Usually relatively mild

Onchocerca volvulus

→ Microfilariae in skin and ocular tissues

→ Severe pruritic dermatitis

→ Subcutaneous nodules

→ Ocular disease

→ River blindness

High-Yield Clinical Pattern

Patient from a filariasis-endemic region

• ●

Mild or asymptomatic infection

• ●

Pruritic or hypopigmented dermatitis

• ●

Microfilariae in blood or skin depending on species

→ Think Mansonella species

Exam Essentials

Genus: Mansonella

Type: Filarial nematode

Disease: Mansonellosis

Major species: M. ozzardi, M. perstans, M. streptocerca

M. ozzardi geography: Central/South America and Caribbean

M. perstans geography: Primarily Africa, with historical South American distribution

M. streptocerca geography: West and Central Africa

Vectors: Biting midges and, in some transmission cycles, blackflies

Typical severity: Usually mild or asymptomatic

Skin manifestations: Pruritus and hypopigmented dermatitis

M. ozzardi microfilariae: Blood

M. perstans microfilariae: Blood

M. streptocerca microfilariae: Skin

Diagnosis: Blood examination or skin examination depending on species, histopathology, supportive serology

Source treatment: Diethylcarbamazine

Additional treatment: Possible role for doxycycline

Prevention: Avoid bites from transmitting insects

Key clinical pearl: The most useful distinction among Mansonella species is where the microfilariae are found: M. ozzardi and M. perstans are primarily detected in blood, whereas M. streptocerca is primarily detected in the skin and can produce a pruritic, hypopigmented dermatitis resembling mild onchocerciasis.

Infectious Disease and Microbiology – Malassezia Species

Overview

Malassezia species are lipophilic yeasts that normally colonize human skin but can cause superficial and, less commonly, invasive infections. Important species include Malassezia furfur, M. pachydermatis, and M. sympodialis.

The most familiar clinical manifestation is pityriasis versicolor, formerly called tinea versicolor. Invasive infection is particularly associated with neonates, immunocompromised patients, central venous catheters, and lipid-containing total parenteral nutrition (TPN).

Classification

Genus: Malassezia

Important species:

• M. furfur

• M. pachydermatis

• M. sympodialis

Type: Lipophilic yeast

Microbiologic Characteristics

Malassezia species are:

• Yeasts

• Lipophilic

• Normal components of the cutaneous microbiota

• Particularly associated with lipid-rich areas of the skin

Because most Malassezia species require or strongly prefer external lipids for growth, laboratory culture may require:

Lipid supplementation of the culture medium

This requirement is an important microbiologic clue.

Historical Terminology

M. furfur was previously associated with the names:

Pityrosporum orbiculare

and

Pityrosporum ovale

These older names may still appear in historical literature.

Incubation Period

The incubation period is:

Unknown

Superficial disease often reflects overgrowth of an organism already present on the skin rather than acquisition followed by a clearly defined incubation period.

Epidemiology

Malassezia species have a:

Worldwide distribution

They commonly colonize human skin without producing disease.

Risk Factors for Invasive Infection

Important risk factors include:

• Total parenteral nutrition (TPN)

• Intravenous lipid emulsions

• Central venous catheters

• Prematurity

• Low birth weight

• Immunocompromised state

• Cushing syndrome

The association between Malassezia and lipid-containing intravenous therapy is particularly important.

Pityriasis Versicolor

The most common superficial infection associated with Malassezia, especially M. furfur, is:

Pityriasis versicolor

This condition was historically called:

Tinea versicolor

Despite the older name, it is caused by a yeast rather than a dermatophyte.

Clinical Manifestations

Pityriasis versicolor typically produces:

• Hypopigmented or hyperpigmented macules

• Fine scaling

• Multiple coalescing lesions

• Minimal inflammation

• Occasional mild pruritus

Commonly affected areas include:

• Upper trunk

• Chest

• Back

• Shoulders

• Neck

Pathogenesis

The organism normally exists as part of the skin microbiota.

Under favorable conditions:

Normal cutaneous colonization

↓

Increased Malassezia proliferation

↓

Transition toward pathogenic growth

↓

Superficial infection of the stratum corneum

↓

Pityriasis versicolor

Warm, humid, and lipid-rich environments can favor proliferation.

Classic Microscopic Appearance

Direct examination of skin scrapings classically demonstrates:

Short curved hyphae + clusters of yeast cells

This produces the famous appearance:

“Spaghetti and meatballs”

This is one of the most important examination associations with Malassezia.

Diagnosis of Pityriasis Versicolor

Diagnosis is often clinical and can be supported by:

• Skin scraping

• KOH preparation

• Microscopic demonstration of yeast and short hyphal elements

Culture is usually unnecessary for straightforward pityriasis versicolor.

Systemic Malassezia Infection

Although much less common, Malassezia can produce:

Fungemia and other invasive infections

These infections occur particularly in:

• Premature neonates

• Low-birth-weight infants

• Immunocompromised patients

• Patients receiving lipid-containing TPN

• Patients with central venous catheters

TPN-Associated Fungemia

A classic invasive-disease pattern is:

Central venous catheter

• ●

Lipid-rich TPN

• ●

Persistent fungemia

→ Consider Malassezia

The organism’s lipophilic nature explains its strong association with intravenous lipid emulsions.

Malassezia furfur

M. furfur can cause:

• Pityriasis versicolor

• Catheter-associated fungemia

• Systemic infection

• Peritonitis

• Rare pneumonia

Invasive disease is particularly associated with immunocompromised patients and neonates receiving intravenous lipid-containing solutions.

Peritonitis

Patients undergoing:

Continuous ambulatory peritoneal dialysis

may rarely develop Malassezia-associated:

Peritonitis

The peritoneal dialysis catheter can act as a foreign-body surface supporting persistent infection.

Malassezia pachydermatis

M. pachydermatis is particularly associated with animals, especially dogs, but can occasionally cause human infection.

The source describes systemic infection in:

Low-birth-weight infants receiving lipid emulsions through central venous catheters

Thus, neonatal intensive-care settings are an important context for recognizing this organism.

Malassezia sympodialis

M. sympodialis commonly colonizes human skin.

The source describes its role as a cause of human disease as uncertain, although Malassezia taxonomy and understanding of individual species’ clinical significance have continued to evolve.

Diagnosis of Invasive Infection

Blood Culture

Blood culture may identify the organism, but Malassezia can be difficult to recover using routine culture conditions.

Because of its lipid dependence:

Lipid-enriched culture conditions may be required

Therefore, when Malassezia fungemia is suspected, communication with the microbiology laboratory can be important.

High-Yield Diagnostic Clue

Premature neonate

• ●

Central venous catheter

• ●

Lipid-containing TPN

• ●

Unexplained fungemia

→ Think Malassezia

Treatment of Pityriasis Versicolor

Superficial pityriasis versicolor can be treated with:

Topical antifungal therapy

or, when appropriate:

Systemic azole therapy

Azole Therapy

The source describes:

Itraconazole 200 mg orally once daily for 7 days

as an effective systemic regimen.

It also describes a historical shorter regimen of:

Itraconazole 400 mg as a single dose

for some patients.

Systemic therapy is generally reserved for extensive, recurrent, or difficult-to-treat disease rather than routine limited infection.

Topical Treatment

Topical therapies are generally preferred for uncomplicated localized disease.

The source specifically lists:

Selenium sulfide 2.5%

applied once daily for approximately 30 minutes for:

2 weeks

as an effective treatment.

Topical azole antifungals are also commonly used.

Recurrence

Pityriasis versicolor can:

Recur frequently

because Malassezia remains part of the normal skin microbiota even after successful treatment.

Residual abnormalities in skin pigmentation may persist for some time after the fungal infection has been eradicated.

Treatment of Systemic Infection

Invasive Malassezia infection requires systemic antifungal therapy.

The source describes:

Intravenous azole treatment

together with:

Removal of the central venous catheter

Source Control

An especially important management principle is:

Remove the infected catheter

and, when clinically possible:

Stop or reduce lipid-containing infusions

because the catheter and lipid-rich environment can promote continued fungal growth.

Treatment Principle

Systemic Malassezia infection

↓

Systemic antifungal therapy

• ●

Central catheter removal

• ●

Address lipid-containing infusion when possible

→ Improved source control

Malassezia vs. Dermatophytes

Malassezia

→ Lipophilic yeast

→ Normal skin flora

→ Pityriasis versicolor

→ “Spaghetti and meatballs” appearance

→ Can cause TPN-associated fungemia

Dermatophytes

→ Filamentous fungi

→ Trichophyton, Microsporum, Epidermophyton

→ Cause true tinea infections

→ Infect keratinized skin, hair, and/or nails

Therefore, the historical term “tinea versicolor” can be misleading because pityriasis versicolor is not a dermatophyte infection.

High-Yield Clinical Pattern

Hypopigmented or hyperpigmented finely scaling patches on the trunk

• ●

KOH showing short hyphae and clusters of yeast

• ●

“Spaghetti and meatballs”

→ Think Malassezia furfur

→ Pityriasis versicolor

Alternative High-Yield Pattern

Premature or immunocompromised patient

• ●

Central venous catheter

• ●

Lipid-containing TPN

• ●

Fungemia

→ Think Malassezia species

Exam Essentials

Genus: Malassezia

Important species: M. furfur, M. pachydermatis, M. sympodialis

Type: Lipophilic yeast

Distribution: Worldwide

Normal habitat: Human skin

Culture requirement: Lipid supplementation may facilitate growth

Classic superficial disease: Pityriasis versicolor

Older name: Tinea versicolor

Classic microscopy: “Spaghetti and meatballs”

Systemic risk factors: Prematurity, immunosuppression, central venous catheter and lipid-containing TPN

Systemic disease: Fungemia and other catheter-associated infections

Other infections: Peritoneal dialysis-associated peritonitis and rare pneumonia

Diagnosis of superficial disease: KOH examination

Diagnosis of fungemia: Blood culture using appropriate lipid-containing conditions

Superficial treatment: Topical azoles or selenium sulfide; systemic azoles for selected cases

Invasive treatment: Systemic antifungal therapy plus catheter removal/source control

Key clinical pearl: Malassezia has two classic examination patterns: “spaghetti and meatballs” on KOH in a patient with pityriasis versicolor, and catheter-associated fungemia in a premature or immunocompromised patient receiving lipid-rich TPN.

Infectious Disease and Microbiology – Madurella Species

Overview

Madurella species are filamentous fungi that are important causes of eumycetoma, a chronic localized fungal infection involving the skin and subcutaneous tissues. The main species include Madurella grisea and Madurella mycetomatis.

These fungi are found in soil and other environmental material, particularly in tropical and subtropical areas. Infection usually follows traumatic implantation of fungal elements into the skin.

Classification

Genus: Madurella

Species: M. grisea, M. mycetomatis

Type: Filamentous fungus (mold)

Major disease: Eumycetoma

Microbiologic Characteristics

Madurella species are filamentous molds with septate hyphae.

They are environmental fungi commonly associated with:

• Soil

• Plant material

• Organic debris

Within infected tissue, fungal elements may organize into compact structures known as grains or granules, which can sometimes be seen directly in drainage from sinus tracts.

Incubation Period

The incubation period is generally:

Months

Because the infection progresses slowly, symptoms may develop gradually over a prolonged period after traumatic inoculation.

Epidemiology

Madurella fungi are widespread in nature, but symptomatic infection is relatively uncommon.

Most cases occur in:

• Tropical regions

• Subtropical regions

• Northern Africa

• Southern Asia

• Central America

Madurella mycetomatis is an especially important cause of eumycetoma in endemic regions.

Transmission

Infection usually occurs through:

Traumatic implantation of contaminated soil or plant material into the skin

Common exposures include:

• Thorn injuries

• Splinters

• Puncture wounds

• Walking barefoot in endemic areas

The foot is the most commonly affected site.

Clinical Infection

The characteristic infection caused by Madurella species is:

Eumycetoma

This is a chronic, slowly progressive infection that may involve:

• Skin

• Subcutaneous tissue

• Fascia

• Bone in advanced disease

Classic Triad of Mycetoma

The classic clinical triad is:

Subcutaneous swelling

• ●

Draining sinus tracts

• ●

Grains or granules in the discharge

This pattern is highly suggestive of mycetoma.

Madura Foot

When mycetoma involves the foot, it is commonly called:

Madura foot

The affected foot may gradually become enlarged and distorted because of chronic inflammation, fibrosis, sinus tract formation, and progressive extension into deeper tissues.

Clinical Manifestations

Possible findings include:

• Chronic localized swelling

• Subcutaneous nodules

• Multiple sinus tracts

• Purulent drainage

• Visible fungal grains

• Progressive tissue destruction

Common sites include:

• Foot

• Ankle

• Tibial region

Osteomyelitis

Advanced infection may extend into underlying bone and produce:

Osteomyelitis

Bone involvement indicates more extensive disease and can make treatment more difficult.

Pathogenesis

The typical sequence is:

Puncture wound with contaminated soil or vegetation

↓

Fungal implantation into subcutaneous tissue

↓

Chronic granulomatous inflammation

↓

Formation of fungal grains

↓

Draining sinus tracts

↓

Extension into deeper tissues

↓

Possible osteomyelitis

Diagnosis

Diagnosis can be made by:

• Culture of affected tissue

• Histopathologic examination

• Examination of grains in drainage

• Imaging when deep extension is suspected

Fungal Culture

The source emphasizes:

Isolation of the fungus from affected tissue

Culture helps identify the organism and distinguish fungal eumycetoma from bacterial actinomycetoma.

Granules

A particularly important diagnostic clue is the presence of:

Visible grains in purulent discharge

The grains may be large enough to see without microscopy.

Their appearance can help suggest the causative organism.

Histopathology

Biopsy may demonstrate:

• Chronic granulomatous inflammation

• Fungal grains

• Septate fungal hyphae

Histology is especially helpful if culture is negative or tissue involvement is extensive.

Imaging

Imaging can help determine the extent of disease and identify:

• Deep soft-tissue involvement

• Sinus tract extension

• Bone destruction

• Osteomyelitis

MRI may be particularly useful for evaluating advanced disease.

Treatment

The source lists:

Ketoconazole

as treatment.

Ketoconazole is now largely of historical importance because systemic use is limited by toxicity and the availability of safer antifungal agents.

Additional Treatment

The source also lists:

Itraconazole

Itraconazole is commonly used for eumycetoma caused by Madurella species, often for a prolonged period because the infection is chronic.

Surgical Management

Surgical treatment may include:

• Excision of localized lesions

• Debridement of infected tissue

• Removal of necrotic tissue

More extensive surgery may be necessary when there is severe soft-tissue destruction or bone involvement.

Treatment Principle

Management often requires:

Prolonged antifungal therapy

• ●

Surgical excision or debridement when needed

Long-term follow-up is important because recurrence can occur.

Prevention

Prevention focuses on reducing traumatic inoculation.

Useful measures include:

• Wearing protective footwear

• Avoiding walking barefoot in endemic areas

• Avoiding thorn and puncture injuries

• Cleaning penetrating wounds promptly

• Wearing protective gloves when handling vegetation

Eumycetoma vs. Actinomycetoma

Eumycetoma

→ Caused by fungi

→ Madurella is an important cause

→ Usually slowly progressive

→ Treated with antifungal therapy and often surgery

Actinomycetoma

→ Caused by filamentous bacteria

→ Often more inflammatory and aggressive

→ Treated primarily with antibacterial therapy

High-Yield Clinical Pattern

Patient from a tropical or subtropical region

• ●

History of puncture wound or barefoot exposure

• ●

Chronic swelling of the foot

• ●

Multiple draining sinus tracts

• ●

Visible grains in discharge

→ Think Madurella species

→ Eumycetoma / Madura foot

Exam Essentials

Organisms: Madurella grisea, Madurella mycetomatis

Type: Filamentous mold

Major disease: Eumycetoma

Environment: Soil and plant material

Geography: Tropical and subtropical regions

Transmission: Traumatic implantation

Most common site: Foot

Classic triad: Swelling + draining sinus tracts + grains

Major complication: Osteomyelitis

Diagnosis: Culture, histopathology, examination of grains

Source treatment: Ketoconazole

Additional treatment: Itraconazole and surgical removal

Prevention: Avoid puncture wounds and use protective footwear

Key clinical pearl: Madurella species classically cause eumycetoma of the foot after traumatic implantation from soil. The most important pattern is chronic swelling, draining sinus tracts, and visible fungal grains, with osteomyelitis occurring in advanced disease.

Infectious Disease and Microbiology – Human T-Lymphotropic Viruses (HTLV-1 and HTLV-2)

Overview

Human T-lymphotropic viruses HTLV-1 and HTLV-2 are enveloped retroviruses with single-stranded positive-sense RNA genomes. They infect human T lymphocytes and can establish lifelong infection.

HTLV-1 is clearly associated with several important diseases, particularly adult T-cell leukemia/lymphoma (ATLL) and HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). By contrast, HTLV-2 has not been firmly linked to a comparable specific malignant disease.

Classification

Viruses: HTLV-1 and HTLV-2

Group: Human T-lymphotropic viruses

Family: Retroviridae

Type: Retroviruses

The historical term “human T-lymphocyte virus” is still commonly used, but “human T-lymphotropic virus” is the standard modern wording.

Microbiologic Characteristics

HTLV-1 and HTLV-2 are:

• Single-stranded positive-sense RNA viruses

• Enveloped

• Retroviruses

• Capable of reverse transcription

• Able to integrate viral DNA into the host-cell genome

Like other retroviruses, they use:

Reverse transcriptase

to convert viral RNA into DNA.

Viral Replication

The general retroviral sequence is:

Viral RNA

↓

Reverse transcription

↓

Proviral DNA

↓

Integration into host genome

↓

Persistent infection of host cells

This ability to integrate into host DNA contributes to lifelong infection.

Incubation and Latency

A precise incubation period is:

Not well defined

For HTLV-1–associated diseases, the interval between infection and clinical disease can be:

Many years to decades

Only a minority of infected individuals develop major HTLV-1–associated complications.

Epidemiology

HTLV infection occurs in multiple regions worldwide.

HTLV-1 is particularly endemic in:

• Southwestern Japan

• The Caribbean

• Parts of sub-Saharan Africa

• Parts of South America

• Other geographically clustered populations

The source specifically highlights high HTLV-1 seropositivity in:

Southeastern Japanese islands and the Caribbean basin

HTLV-2 Epidemiology

HTLV-2 has been detected in several populations and has historically had a strong association with:

Injection drug use

The virus has also been identified in certain indigenous populations.

Transmission

HTLV can be transmitted through infected lymphocytes in:

• Sexual contact

• Blood exposure

• Sharing contaminated injection equipment

• Mother-to-child transmission

Mother-to-child transmission occurs especially through:

Breastfeeding

Prevention Principle

The source states that prevention resembles that used for HIV.

Important preventive measures therefore include:

• Safer-sex practices

• Avoidance of shared needles or injection equipment

• Screening of blood products where applicable

• Prevention of mother-to-child transmission in appropriate settings

HTLV-1 Infection

Major Disease Associations

HTLV-1 is associated with:

Adult T-cell leukemia/lymphoma

and

HTLV-1–associated myelopathy/tropical spastic paraparesis

Other inflammatory and infectious associations can also occur.

Adult T-Cell Leukemia/Lymphoma

Major Malignancy

One of the classic complications of HTLV-1 is:

Adult T-cell leukemia/lymphoma (ATLL)

This is a malignancy of mature T lymphocytes.

Clinical Features

ATLL may present with:

• Lymphadenopathy

• Skin lesions

• Hepatosplenomegaly

• Circulating abnormal T cells

• Immunosuppression

• Opportunistic infections

A particularly important metabolic complication is:

Hypercalcemia

High-Yield ATLL Pattern

Adult from an HTLV-1 endemic region

• ●

T-cell malignancy

• ●

Hypercalcemia

• ●

Characteristic abnormal lymphocytes

→ Think HTLV-1–associated adult T-cell leukemia/lymphoma

Flower Cells

Peripheral blood may show atypical lymphocytes with multilobulated nuclei classically called:

“Flower cells”

This is a memorable hematologic association with ATLL.

HTLV-1–Associated Myelopathy

HAM/TSP

HTLV-1 can cause a chronic progressive neurologic syndrome known as:

HTLV-1–associated myelopathy

or:

Tropical spastic paraparesis

abbreviated:

HAM/TSP

Clinical Manifestations

HAM/TSP typically causes:

• Slowly progressive weakness of both legs

• Spastic paraparesis

• Hyperreflexia

• Gait impairment

• Urinary dysfunction

• Sensory symptoms of variable severity

The condition usually evolves gradually rather than as an acute myelitis.

High-Yield Neurologic Pattern

HTLV-1 exposure

• ●

Slowly progressive bilateral leg weakness

• ●

Spasticity and hyperreflexia

• ●

Bladder dysfunction

→ Think HAM/TSP

Infective Dermatitis

The source lists:

Jamaican infectious dermatitis

This is more commonly referred to as:

HTLV-1–associated infective dermatitis

It is a chronic relapsing dermatitis, particularly recognized in children in HTLV-1 endemic areas.

Strongyloides Association

HTLV-1 infection is also clinically important because it is associated with increased susceptibility to severe or persistent:

Strongyloides stercoralis infection

This interaction can complicate treatment and increase the risk of severe strongyloidiasis.

HTLV-2

Clinical Significance

The source states that:

No disease has been conclusively causally associated with HTLV-2

HTLV-2 was initially isolated from patients with hairy-cell leukemia, but this association was not established as causal.

HTLV-2 Today

HTLV-2 infection is generally considered less pathogenic than HTLV-1.

Some neurologic or inflammatory associations have been reported, but there is no classic disease syndrome equivalent to:

HTLV-1 → ATLL or HAM/TSP

Diagnosis

The source lists:

• Cell culture

• Serology

• Antigen detection

In modern practice, diagnosis is primarily based on:

Serologic testing

with confirmatory testing when required.

Serology

Screening tests detect:

Antibodies against HTLV

Positive screening results may require confirmatory assays to distinguish:

HTLV-1

from:

HTLV-2

Molecular Testing

PCR can detect:

Proviral HTLV DNA

and may help confirm infection or distinguish HTLV-1 from HTLV-2 in selected circumstances.

Treatment

HTLV Infection Itself

The source describes treatment as:

Symptomatic

There is no standard therapy that reliably eradicates integrated HTLV infection from the body.

Management therefore focuses largely on treating:

HTLV-associated diseases

rather than eliminating the latent virus itself.

Adult T-Cell Leukemia/Lymphoma Treatment

Management of ATLL depends on its clinical subtype and severity and may involve:

• Antineoplastic chemotherapy

• Antiviral-based approaches in selected forms

• Targeted therapy

• Hematopoietic stem-cell transplantation in selected patients

This requires specialist hematology/oncology management.

HAM/TSP Treatment

Treatment is generally aimed at:

Reducing inflammation and controlling symptoms

No therapy reliably reverses established neurologic damage in all patients.

Supportive treatment may include:

• Management of spasticity

• Physical rehabilitation

• Bladder management

• Pain management

Prevention

Because HTLV spreads through infected lymphocytes, preventive strategies resemble those used for other blood-borne and sexually transmitted retroviruses.

Important measures include:

• Safer sexual practices

• Avoiding shared injection equipment

• Appropriate blood-donor screening

• Prevention of mother-to-child transmission

Breastfeeding and Transmission

Prolonged breastfeeding is an important route of:

HTLV-1 mother-to-child transmission

In endemic areas, prevention strategies may include modification or avoidance of breastfeeding when appropriate and feasible according to local recommendations.

HTLV-1 vs. HIV

HTLV-1

→ Retrovirus

→ Primarily infects T lymphocytes

→ Promotes T-cell proliferation/transformation

→ Adult T-cell leukemia/lymphoma

→ HAM/TSP

→ Often long latency

HIV

→ Retrovirus

→ Progressive destruction and dysfunction of CD4 T cells

→ Acquired immunodeficiency syndrome

→ Opportunistic infections and malignancies

Thus:

HTLV-1 tends to drive T-cell proliferation

whereas:

HIV primarily causes progressive immune deficiency

HTLV-1 vs. HTLV-2

HTLV-1

→ Strong established disease associations

→ ATLL

→ HAM/TSP

→ Infective dermatitis

→ Endemic clusters in Japan, Caribbean and other regions

HTLV-2

→ Frequently associated epidemiologically with injection drug use

→ No classic strongly established malignant syndrome comparable with HTLV-1

→ Generally lower recognized pathogenicity

High-Yield Clinical Pattern

Patient from an HTLV-1 endemic area

• ●

Adult T-cell malignancy

• ●

Hypercalcemia

→ Think HTLV-1 → Adult T-cell leukemia/lymphoma

Alternative High-Yield Pattern

Chronic progressive spastic weakness of both legs

• ●

Hyperreflexia

• ●

Bladder dysfunction

• ●

HTLV-1 exposure

→ Think HTLV-1–associated myelopathy / tropical spastic paraparesis

Exam Essentials

Viruses: HTLV-1 and HTLV-2

Family: Retroviridae

Genome: Positive-sense single-stranded RNA

Envelope: Present

Key enzyme: Reverse transcriptase

Replication: Proviral DNA integrates into host genome

Transmission: Sexual, blood exposure, shared needles, breastfeeding

HTLV-1 endemic regions: Southwestern Japan, Caribbean, parts of Africa and South America

HTLV-2 association: Injection drug use

Major HTLV-1 malignancy: Adult T-cell leukemia/lymphoma

Classic ATLL metabolic finding: Hypercalcemia

Classic ATLL blood cell: Flower cell

Major neurologic disease: HAM/TSP

Dermatologic association: HTLV-1–associated infective dermatitis

Parasitic association: Increased risk of severe/persistent Strongyloides infection

Diagnosis: Primarily serology, with confirmatory/molecular testing as needed

Treatment: Management of specific HTLV-associated disease; no routine curative antiviral eradication therapy

Prevention: Safer sex, blood/injection precautions, and prevention of mother-to-child transmission

Key clinical pearl: HTLV-1 is the retrovirus classically linked to two major examination syndromes: adult T-cell leukemia/lymphoma—often with hypercalcemia and “flower cells”—and a chronic progressive spastic paraparesis known as HAM/TSP. HTLV-2 is epidemiologically associated with injection drug use but has far weaker established disease associations.

Infectious Disease and Microbiology – Lymphocytic Choriomeningitis Virus

Overview

Lymphocytic choriomeningitis virus (LCMV) is an enveloped RNA virus belonging to the family Arenaviridae. It is a rodent-associated zoonotic virus that usually causes either an asymptomatic or mild febrile illness but can occasionally produce aseptic meningitis, meningoencephalitis, or other neurologic disease.

A characteristic diagnostic clue is marked lymphocytic pleocytosis in the cerebrospinal fluid (CSF).

Classification

Virus: Lymphocytic choriomeningitis virus

Abbreviation: LCMV

Family: Arenaviridae

Genus: Mammarenavirus

Major reservoir: House mouse

LCMV is related to other mammarenaviruses, including Lassa virus, but the clinical syndromes are substantially different.

Microbiologic Characteristics

LCMV is:

• Enveloped

• A single-stranded RNA virus

• Characterized by two RNA genome segments

• Helical in nucleocapsid organization

• An arenavirus

The two genome segments are conventionally called:

L segment

and

S segment

Genome

The source describes the genome as:

Two single-stranded, circular RNA segments

More precisely, arenaviruses possess two single-stranded RNA genome segments with an ambisense coding strategy. The genome is segmented but is not generally described as two conventional circular RNA molecules.

Incubation Period

The incubation period is generally approximately:

1–2 weeks

The exact interval can vary depending on the nature and intensity of exposure.

Epidemiology

Human LCMV infection is:

Uncommon

but the virus has a broad geographic distribution because its principal reservoir, the house mouse, is widespread.

Rodent Reservoir

House Mouse

The classic natural reservoir is:

Mus musculus

the:

Common house mouse

Chronically infected mice may shed virus in:

• Urine

• Feces

• Saliva

• Other secretions

Other Rodent Exposures

Human infection has also been associated with exposure to infected:

• Pet rodents

• Laboratory rodents

• Rodent-contaminated environments

Thus, a history of mouse or other rodent exposure is an important epidemiologic clue.

Transmission

Humans may acquire LCMV through exposure to:

Rodent urine, feces, saliva, or contaminated material

Transmission may occur through:

• Inhalation of contaminated particles

• Direct contact with rodent excreta

• Contaminated food or surfaces

• Contact of contaminated material with damaged skin or mucous membranes

Person-to-Person Transmission

Routine person-to-person transmission is not typical.

Important exceptions include:

Mother-to-fetus transmission

and rare transmission through:

Organ transplantation

These routes are particularly important because they can result in severe disease.

Clinical Infection

Many LCMV infections are:

Asymptomatic

or produce a nonspecific influenza-like illness.

When symptomatic, disease can have a biphasic pattern.

Initial Febrile Illness

The first phase may include:

• Fever

• Malaise

• Myalgia

• Headache

• Nausea or vomiting

• Loss of appetite

The source also lists:

• Adenitis

• Skin rash

These manifestations can occur but are less characteristic than the febrile and neurologic syndromes.

Neurologic Disease

Aseptic Meningitis

LCMV is a classic viral cause of:

Aseptic meningitis

Neurologic manifestations can include:

• Severe headache

• Fever

• Neck stiffness

• Photophobia

• Nausea and vomiting

Meningoencephalitis

More extensive CNS involvement can produce:

Meningoencephalitis

with manifestations such as:

• Altered mental status

• Confusion

• Neurologic abnormalities

• Seizures in severe cases

CSF Findings

Lymphocytic Pleocytosis

A particularly characteristic finding is:

Significant lymphocytic pleocytosis

in the CSF.

This means that CSF contains an increased number of white blood cells with a predominance of:

Lymphocytes

Typical CSF Pattern

LCMV meningitis may demonstrate:

Elevated CSF white blood cells

• ●

Lymphocyte predominance

• ●

Elevated protein

• ●

Glucose that may be reduced

The possibility of low CSF glucose is notable because it can complicate differentiation from bacterial, fungal, or tuberculous meningitis.

High-Yield Meningitis Pattern

Rodent exposure

• ●

Febrile illness

• ●

Aseptic meningitis

• ●

Marked lymphocytic CSF pleocytosis

→ Think LCMV

Congenital LCMV Infection

Important Clinical Association

Maternal infection during pregnancy can result in:

Congenital LCMV infection

The virus can cross the placenta and cause severe fetal CNS and ocular abnormalities.

Congenital Manifestations

Important abnormalities can include:

• Hydrocephalus

• Microcephaly

• Intracranial calcifications

• Chorioretinitis

• Visual impairment

• Neurodevelopmental abnormalities

Congenital infection is an important but often underrecognized manifestation of LCMV.

High-Yield Congenital Pattern

Maternal rodent exposure

• ●

Congenital hydrocephalus

• ●

Chorioretinitis

• ●

Intracranial abnormalities

→ Consider congenital LCMV infection

Transplant-Associated Infection

LCMV has rarely been transmitted through:

Solid-organ transplantation

In immunosuppressed transplant recipients, infection can be severe and potentially fatal.

This is a very different clinical setting from the usually self-limited infection occurring in immunocompetent individuals.

Diagnosis

The source lists:

• Cell culture

• Serology

Serology

Detection of LCMV-specific antibodies can support the diagnosis.

Serologic testing is particularly useful when interpreted together with:

Compatible neurologic disease + rodent exposure

Molecular Diagnosis

Molecular testing using:

RT-PCR

may detect viral RNA in appropriate clinical specimens, particularly in specialized/reference laboratory settings.

Cell Culture

LCMV can be isolated in cell culture, but routine clinical diagnosis generally does not depend on viral culture because specialized laboratory procedures and biosafety precautions are required.

Treatment

The source recommends:

Symptomatic treatment

For most immunocompetent patients:

Supportive care

is the mainstay of management.

Supportive Management

Treatment may include:

• Hydration

• Analgesia

• Antipyretic therapy

• Management of nausea and vomiting

• Neurologic monitoring in meningitis or encephalitis

• Seizure management when necessary

There is no established routine antiviral treatment for uncomplicated LCMV infection.

Prevention

Prevention primarily involves reducing exposure to:

Rodents and rodent excreta

Important measures include:

• Rodent control in homes

• Safe food storage

• Avoiding direct contact with wild mice

• Appropriate cleaning of rodent-contaminated environments

• Careful handling of pet and laboratory rodents

Pregnant individuals should be particularly cautious about exposure to potentially infected rodents because of the risk of congenital infection.

LCMV vs. Lassa Virus

Lymphocytic choriomeningitis virus

→ Arenavirus

→ House mouse reservoir

→ Usually mild febrile illness or aseptic meningitis

→ Marked lymphocytic CSF pleocytosis

→ Congenital CNS/ocular disease possible

→ Treatment primarily supportive

Lassa virus

→ Arenavirus

→ Mastomys multimammate rat reservoir

→ West Africa

→ Lassa hemorrhagic fever

→ Sensorineural hearing loss is an important complication

→ Ribavirin has historically been used in treatment

High-Yield Clinical Pattern

Mouse/rodent exposure

• ●

Biphasic febrile illness

• ●

Meningitis or meningoencephalitis

• ●

Marked lymphocytic pleocytosis in CSF

→ Think Lymphocytic choriomeningitis virus

Exam Essentials

Virus: Lymphocytic choriomeningitis virus (LCMV)

Family: Arenaviridae

Genus: Mammarenavirus

Genome: Two single-stranded RNA segments

Coding strategy: Ambisense

Envelope: Present

Nucleocapsid: Helical

Major reservoir: House mouse (Mus musculus)

Transmission: Exposure to infected rodent excreta/secretions

Frequency: Rare human infection

Major neurologic disease: Aseptic meningitis/meningoencephalitis

Classic CSF finding: Marked lymphocytic pleocytosis

Congenital disease: Hydrocephalus, chorioretinitis and other CNS abnormalities

Diagnosis: Serology, molecular testing such as RT-PCR, specialized viral culture

Treatment: Supportive/symptomatic

Prevention: Rodent control and avoidance of rodent excreta

Key clinical pearl: Think of LCMV when a patient with mouse or rodent exposure develops a febrile illness followed by aseptic meningitis with prominent lymphocytic CSF pleocytosis. Also remember LCMV as an important congenital infection associated particularly with hydrocephalus and chorioretinitis.

Medicine – Friedreich Ataxia

Friedreich ataxia is an inherited progressive neurodegenerative disorder that primarily affects the spinal cord, peripheral nerves, and cerebellar pathways. It is one of the most important hereditary causes of ataxia beginning in childhood or adolescence.

The disorder produces a characteristic combination of progressive gait and limb ataxia, sensory neuropathy, pyramidal tract abnormalities, skeletal deformities, cardiomyopathy, and an increased risk of diabetes mellitus.

1. Inheritance

Friedreich ataxia is inherited in an autosomal recessive pattern.

This means that an affected person usually inherits one abnormal allele from each parent, while the parents are typically unaffected carriers.

Therefore, affected siblings may occur in the same family even when the parents have no neurological symptoms.

2. Genetic Abnormality

Friedreich ataxia is caused by pathogenic variants in the FXN gene on chromosome 9.

The most common abnormality is a GAA trinucleotide-repeat expansion within the FXN gene.

This leads to reduced production of the protein:

Frataxin.

3. Frataxin

Frataxin is a mitochondrial protein involved particularly in iron–sulfur cluster formation and normal mitochondrial energy metabolism.

Reduced frataxin causes mitochondrial dysfunction, abnormal iron handling, oxidative injury, and progressive cellular damage.

Tissues with high metabolic requirements are particularly affected, including:

Nervous system.

Heart.

Pancreatic beta cells.

This helps explain the combination of neurological disease, cardiomyopathy, and diabetes.

4. Age at Onset

Friedreich ataxia usually begins in childhood or adolescence.

An average onset around 10–15 years is often quoted, so the original figure of approximately 12 years is reasonable as a typical teaching value.

However, age at onset is variable, and some patients present later in adulthood.

Earlier onset is often associated with more severe disease.

5. Neurological Pathology

Friedreich ataxia affects several neurological pathways simultaneously.

Important structures include:

Dorsal columns of the spinal cord.

Spinocerebellar tracts.

Corticospinal tracts.

Peripheral sensory nerves and dorsal root ganglia.

This combination explains why patients may have both ataxic features and pyramidal signs, together with peripheral sensory abnormalities.

6. Ataxia

Progressive ataxia is the central neurological feature.

Patients commonly first develop difficulty with:

Walking.

Running.

Balance.

Coordination.

The gait becomes broad-based and unsteady.

As the disorder progresses, the upper limbs may also become ataxic, interfering with writing, eating, and other fine motor tasks.

7. Cerebellar-Type Signs

Patients may demonstrate several signs commonly associated with cerebellar dysfunction.

These can include:

Gait ataxia.

Limb incoordination.

Dysmetria.

Dysarthria.

However, the ataxia in Friedreich disease is not due solely to primary cerebellar degeneration. Loss of proprioceptive information from the dorsal columns and peripheral sensory nerves contributes substantially.

Therefore, it is better regarded as a mixed sensory and spinocerebellar ataxia.

8. Loss of Proprioception

Damage to the dorsal columns and large sensory fibres leads to impaired:

Joint-position sense.

Vibration sensation.

This produces sensory ataxia in addition to the spinocerebellar component.

Patients may therefore become especially unstable when visual input is removed, and a positive Romberg sign can occur.

9. Peripheral Neuropathy

A peripheral sensory neuropathy is common.

Patients may develop:

Reduced vibration sensation.

Reduced proprioception.

Distal sensory impairment.

Absent or reduced tendon reflexes, particularly at the ankles and knees.

This peripheral neuropathy contributes significantly to the gait disturbance.

10. Pyramidal Tract Involvement

The corticospinal tracts may also be affected.

This can produce upper motor neurone features such as:

Extensor plantar responses.

Weakness.

Increased tone or spasticity in some patients.

This creates an important mixed neurological pattern because tendon reflexes may be reduced from peripheral neuropathy while Babinski responses remain extensor because of corticospinal tract disease.

11. Spastic Paraparesis

As the disease advances, weakness and corticospinal tract involvement may result in spastic paraparesis, meaning bilateral weakness of the legs with pyramidal tract involvement.

However, the neurological picture is often mixed rather than a pure spastic paraparesis because peripheral neuropathy and sensory pathway degeneration occur simultaneously.

12. Reflex Pattern

A characteristic examination combination may be:

Absent lower-limb tendon reflexes.

with

Extensor plantar responses.

At first this may seem contradictory.

It occurs because:

Peripheral nerve involvement → reduced tendon reflexes.

while

Corticospinal tract involvement → extensor plantar responses.

This mixed pattern is an important clue to Friedreich ataxia.

13. Pes Cavus

Pes cavus means an abnormally high arch of the foot.

It is common in Friedreich ataxia and develops in association with chronic neuromuscular imbalance.

Other foot deformities may also develop.

Therefore:

Young patient + progressive ataxia + pes cavus → consider Friedreich ataxia.

14. Kyphoscoliosis

Spinal deformity is common.

Patients may develop:

Scoliosis.

Kyphosis.

or

Kyphoscoliosis.

These deformities may become clinically important as the disease progresses and can contribute to impaired posture and respiratory mechanics.

15. High-Arched Palate

A high-arched palate has traditionally been described among the physical features of Friedreich ataxia.

It may form part of the skeletal phenotype but is much less diagnostically important than:

Progressive ataxia.

Pes cavus.

Scoliosis.

Neuropathy.

Cardiomyopathy.

16. Cardiomyopathy

Cardiac involvement is one of the most important non-neurological manifestations of Friedreich ataxia.

Cardiomyopathy is common and may significantly influence prognosis.

The classic cardiac abnormality is hypertrophic cardiomyopathy, although other patterns can occur.

Patients may develop:

Palpitations.

Dyspnoea.

Chest symptoms.

Arrhythmias.

Heart failure in advanced disease.

Regular cardiac assessment is therefore important.

17. Diabetes Mellitus

Friedreich ataxia is associated with abnormalities of glucose metabolism.

Some patients develop:

Impaired glucose tolerance.

or

Diabetes mellitus.

This is related partly to mitochondrial dysfunction involving pancreatic beta cells and insulin metabolism.

Therefore, metabolic monitoring forms part of long-term care.

18. Other Clinical Features

Other manifestations may include:

Dysarthria.

Nystagmus or abnormal eye movements.

Optic neuropathy in some patients.

Hearing impairment in some cases.

Muscle weakness and wasting as disease advances.

The exact phenotype and severity vary considerably between individuals.

19. Diagnosis

Diagnosis is primarily confirmed by genetic testing of the FXN gene, particularly testing for the characteristic GAA repeat expansion.

The clinical picture provides important clues, especially when a young patient has:

Progressive ataxia + sensory neuropathy + absent reflexes + extensor plantar responses + pes cavus/scoliosis + cardiomyopathy.

20. Investigations

Investigations may include:

Genetic testing → confirms FXN-related disease.

ECG and echocardiography → assess cardiac involvement.

Blood glucose or HbA1c → screen for diabetes.

Nerve-conduction studies → demonstrate sensory neuropathy.

MRI → may help exclude alternative neurological disorders and can show spinal cord changes.

21. Treatment

Management is multidisciplinary because Friedreich ataxia affects several organ systems.

Treatment may include:

Physiotherapy and rehabilitation.

Mobility and occupational support.

Management of scoliosis and foot deformities.

Cardiac surveillance and treatment.

Diabetes screening and treatment.

Speech and swallowing assessment when required.

Disease-modifying therapies have also emerged for selected patients in some jurisdictions, but supportive multidisciplinary care remains essential.

22. Friedreich Ataxia – Note Form

Type: hereditary progressive ataxia.

Inheritance: autosomal recessive.

Gene: FXN on chromosome 9.

Common genetic abnormality: GAA trinucleotide-repeat expansion.

Protein affected: frataxin.

Main mechanism: reduced frataxin → mitochondrial dysfunction and progressive neuronal/cardiac injury.

Typical onset: childhood or adolescence, often around the early teenage years.

Ataxia: progressive gait and limb incoordination.

Sensory involvement: loss of vibration and joint-position sense.

Peripheral neuropathy: commonly sensory, causing reduced or absent tendon reflexes.

Pyramidal involvement: extensor plantar responses ± spasticity and weakness.

Skeletal abnormalities: pes cavus, scoliosis/kyphoscoliosis and sometimes high-arched palate.

Cardiac involvement: cardiomyopathy, classically hypertrophic, with possible arrhythmias.

Metabolic association: impaired glucose tolerance and diabetes mellitus.

23. Characteristic Examination Pattern

A particularly useful neurological combination is:

Progressive ataxia.

Loss of proprioception and vibration sensation.

Absent lower-limb reflexes.

Extensor plantar responses.

Pes cavus.

This combination reflects simultaneous damage to:

Peripheral sensory nerves + dorsal columns + spinocerebellar tracts + corticospinal tracts.

Key Clinical Pattern

Think of Friedreich ataxia as:

Autosomal recessive FXN mutation on chromosome 9 → reduced frataxin → mitochondrial dysfunction.

The classic clinical picture is:

Young patient + progressive ataxia + peripheral sensory neuropathy + absent reflexes + extensor plantar responses + pes cavus/kyphoscoliosis + cardiomyopathy ± diabetes.

A particularly high-yield association is:

Friedreich ataxia → neurological disease + skeletal deformity + hypertrophic cardiomyopathy + diabetes mellitus.

Medicine – Visual Field Defects and Lesion Localisation

Visual field defects are important neurological and ophthalmological signs because the pattern of visual loss can help localise a lesion along the visual pathway. A useful first distinction is whether the abnormality affects one eye only or corresponding visual fields of both eyes.

In general:

One-eye defects → think retina or optic nerve.

Both-eye field defects → think optic chiasm or structures behind the chiasm.

1. Visual Pathway

Visual information begins in the retina and travels through the:

Retina → optic nerve → optic chiasm → optic tract → lateral geniculate nucleus → optic radiations → primary visual cortex in the occipital lobe.

At the optic chiasm, fibres arising from the nasal retina cross to the opposite side, whereas fibres from the temporal retina remain uncrossed.

This crossing explains the characteristic visual-field defects produced by lesions at different levels.

2. Lesions Affecting One Eye

Visual loss confined to one eye usually indicates pathology anterior to the optic chiasm.

Possible sites include:

Eye itself.

Retina.

Optic nerve.

The precise visual-field abnormality depends on which structure is affected.

3. Complete Monocular Visual Loss

Complete loss of vision in one eye can occur with severe damage to the ipsilateral optic nerve.

A complete optic nerve transection therefore causes:

Complete blindness of the affected eye.

For example:

Right optic nerve transection → complete right monocular blindness.

The opposite eye remains unaffected if the lesion is confined to the right optic nerve.

4. Other Causes of Severe Monocular Visual Loss

Although optic nerve transection is the classic anatomical example, complete or profound monocular visual loss can also result from severe ocular, retinal, or optic nerve disease.

Important possibilities include:

Central retinal artery occlusion.

Severe optic neuropathy.

Retinal detachment involving the macula.

Major ocular trauma.

Therefore, monocular blindness does not automatically mean that the optic nerve has literally been transected.

5. Central Scotoma

A scotoma is a localized area of reduced or absent vision surrounded by relatively preserved vision.

A central scotoma affects the central part of the visual field and may be experienced as a blurred, dark, or missing area directly in front of the patient.

Central scotomas are particularly associated with diseases affecting the optic nerve or macula.

6. Optic Neuritis

Optic neuritis is an important cause of a central or centrocaecal scotoma.

Typical features include:

Reduced visual acuity.

Central visual-field loss.

Reduced colour vision, particularly red desaturation.

Pain on eye movement.

Relative afferent pupillary defect when unilateral or asymmetric.

Optic neuritis is particularly associated with demyelinating disorders such as multiple sclerosis.

7. Constricted Visual Field

A constricted visual field means that the peripheral visual field progressively narrows while central vision may initially remain relatively preserved.

This may eventually produce tunnel vision.

Important causes include:

Chronic glaucoma.

Chronic papilloedema with secondary optic nerve damage.

Another important cause of progressive peripheral field constriction is retinitis pigmentosa.

8. Chronic Glaucoma

In chronic glaucoma, progressive optic nerve damage produces characteristic visual-field abnormalities.

Early defects may include:

Paracentral scotomas.

Nasal steps.

Arcuate scotomas.

As disease becomes advanced, the remaining visual field may become markedly constricted, producing:

Tunnel vision.

Therefore:

Advanced chronic glaucoma → severe peripheral field constriction.

9. Chronic Papilloedema

Long-standing papilloedema from raised intracranial pressure can eventually damage optic nerve axons.

Early papilloedema often causes an enlarged blind spot, while visual acuity may initially remain relatively preserved.

If papilloedema persists:

Chronic disc swelling → optic nerve damage → secondary optic atrophy → progressive visual-field loss.

Advanced disease can therefore produce substantial field constriction and permanent visual impairment.

10. Lesions Affecting Both Eyes

When a lesion affects corresponding parts of the visual fields of both eyes, pathology at the optic chiasm or behind the chiasm should be considered.

Important sites include:

Optic chiasm.

Optic tract.

Lateral geniculate nucleus.

Optic radiations.

Occipital visual cortex.

The exact field defect helps localise the lesion.

11. Bitemporal Hemianopia

Bitemporal hemianopia means loss of the temporal half of the visual field in both eyes.

This pattern strongly suggests a lesion involving the optic chiasm.

Therefore:

Bitemporal hemianopia → think optic chiasm.

12. Why Chiasmal Lesions Cause Bitemporal Hemianopia

The nasal retinal fibres cross at the optic chiasm.

These nasal retinal fibres carry information from the temporal visual fields.

Compression of the central optic chiasm therefore preferentially damages the crossing nasal fibres.

The result is:

Loss of temporal visual field in both eyes → bitemporal hemianopia.

13. Causes of Chiasmal Lesions

Important causes include:

Pituitary adenoma.

Craniopharyngioma.

Meningioma.

Intracranial aneurysm, depending on its location.

Other suprasellar masses may also compress the optic chiasm.

14. Pituitary Adenoma

A pituitary adenoma is a classic cause of bitemporal hemianopia.

The pituitary gland lies beneath the optic chiasm.

As a pituitary tumour expands upward from the sella turcica, it may compress the inferior aspect of the optic chiasm.

Therefore:

Pituitary mass → optic chiasm compression → bitemporal visual-field loss.

Endocrine abnormalities may coexist depending on whether the tumour secretes hormones or interferes with normal pituitary function.

15. Craniopharyngioma

Craniopharyngiomas are tumours arising in the sellar or suprasellar region.

Because of their proximity to the optic chiasm, they can cause:

Visual-field defects.

Reduced visual acuity.

Endocrine abnormalities.

Symptoms of raised intracranial pressure, particularly with larger lesions.

Bitemporal hemianopia may occur from chiasmal compression.

16. Homonymous Visual-Field Defects

A homonymous visual-field defect affects the same side of the visual field in both eyes.

For example:

Right homonymous hemianopia → loss of the right visual field of both eyes.

This indicates a lesion behind the optic chiasm on the opposite side.

Therefore:

Right homonymous field loss → left retrochiasmal lesion.

Left homonymous field loss → right retrochiasmal lesion.

17. Homonymous Quadrantanopia

A homonymous quadrantanopia means loss of the same quarter of the visual field in both eyes.

This commonly results from a lesion involving part of the optic radiations.

The two important patterns are:

Superior quadrantanopia → temporal lobe lesion.

Inferior quadrantanopia → parietal lobe lesion.

18. Superior Homonymous Quadrantanopia

Fibres carrying information from the superior visual field travel through the inferior optic radiations, which loop anteriorly through the temporal lobe.

This loop is known as Meyer’s loop.

A temporal lobe lesion therefore produces a contralateral superior homonymous quadrantanopia.

A useful memory phrase is:

Temporal lesion → “pie in the sky.”

For example:

Left temporal lobe lesion → right superior homonymous quadrantanopia.

19. Inferior Homonymous Quadrantanopia

Fibres carrying the inferior visual field travel more superiorly through the parietal lobe.

A parietal optic-radiation lesion therefore causes:

Contralateral inferior homonymous quadrantanopia.

A useful memory phrase is:

Parietal lesion → “pie on the floor.”

For example:

Left parietal lesion → right inferior homonymous quadrantanopia.

20. Homonymous Hemianopia

Homonymous hemianopia means loss of the same half of the visual field in both eyes.

It results from a retrochiasmal lesion.

Possible sites include:

Optic tract.

Lateral geniculate nucleus.

Optic radiations.

Occipital cortex.

21. Optic Tract Lesion

An optic tract lesion produces a contralateral homonymous hemianopia.

The defect is often relatively incongruous, meaning that the field defects in the two eyes are not exactly identical in shape or extent.

For example:

Left optic tract lesion → right homonymous hemianopia.

22. Congruity and Lesion Location

As lesions occur farther posteriorly along the visual pathway, homonymous field defects generally become more congruous.

Congruous means that the field defects in the two eyes closely resemble each other.

Therefore, as a general rule:

Anterior retrochiasmal lesion → more incongruous.

Posterior retrochiasmal lesion → more congruous.

This is a useful localisation principle rather than an absolute rule.

23. Lateral Geniculate Lesions

The lateral geniculate nucleus/body is a relay station between the optic tract and optic radiations.

Lesions here can cause a contralateral homonymous visual-field defect, sometimes with characteristic sectoral patterns depending on vascular anatomy.

The original note associates a congruous homonymous hemianopia with a lateral geniculate lesion, but congruity alone does not precisely localise the lesion.

24. Occipital Cortex Lesions

The final part of the visual pathway is the primary visual cortex in the occipital lobe.

An occipital cortex lesion typically causes a highly congruous contralateral homonymous hemianopia.

One particularly important feature is:

Macular sparing.

25. Macular Sparing

Macular sparing means that central vision is preserved despite loss of the surrounding homonymous visual field.

This is classically associated with an occipital cortex lesion, particularly an occipital infarction.

One explanation is that the occipital pole representing central vision may have overlapping vascular supply, although the mechanism is more complex than a simple fixed dual blood supply in every patient.

Therefore:

Homonymous hemianopia + macular sparing → strongly suggests occipital cortex involvement.

26. Visual Field Defects – Note Form

Complete monocular visual loss: severe ipsilateral retinal or optic nerve lesion; complete optic nerve transection is the classic anatomical example.

Central scotoma: optic nerve or macular disease; optic neuritis is an important cause.

Constricted visual field: chronic glaucoma, chronic papilloedema with optic nerve damage, or retinitis pigmentosa.

Bitemporal hemianopia: optic chiasm lesion.

Chiasmal causes: pituitary adenoma, craniopharyngioma, meningioma and other suprasellar masses; some aneurysms may also compress the chiasm.

Superior homonymous quadrantanopia: contralateral temporal lobe/Meyer’s loop lesion.

Inferior homonymous quadrantanopia: contralateral parietal optic-radiation lesion.

Homonymous hemianopia: contralateral lesion behind the optic chiasm.

Incongruous homonymous hemianopia: suggests a relatively anterior retrochiasmal lesion, such as the optic tract.

Increasingly congruous field defects: generally suggest progressively more posterior lesions.

Homonymous hemianopia with macular sparing: classically suggests an occipital cortex lesion.

27. Easy Localisation Sequence

Think of the visual pathway from front to back:

One eye only → retina or optic nerve.

Temporal fields of both eyes lost → optic chiasm.

Same side of visual field lost in both eyes → opposite retrochiasmal pathway.

Superior quadrant lost → opposite temporal lobe.

Inferior quadrant lost → opposite parietal lobe.

Very congruous homonymous hemianopia ± macular sparing → opposite occipital cortex.

Key Clinical Pattern

The most useful rule is:

PRE-CHIASM → ONE EYE.

CHIASM → BITEMPORAL HEMIANOPIA.

POST-CHIASM → CONTRALATERAL HOMONYMOUS FIELD LOSS.

For the optic radiations:

Temporal lobe → superior quadrantanopia → “pie in the sky.”

Parietal lobe → inferior quadrantanopia → “pie on the floor.”

And finally:

Occipital cortex → highly congruous homonymous hemianopia, often with macular sparing.

1. Visual Pathway Visual information begins in the retina and travels through the: Retina → optic nerve → optic chiasm → optic tract → lateral geniculate nucleus → optic radiations → primary visual cortex in the occipital lobe. At the optic chiasm, fibres arising from the nasal retina cross to the opposite side, whereas fibres from the temporal retina remain uncrossed. This crossing explains the characteristic visual-field defects produced by lesions at different levels. 

2. Lesions Affecting One Eye Visual loss confined to one eye usually indicates pathology anterior to the optic chiasm. Possible sites include: Eye itself. Retina. Optic nerve. The precise visual-field abnormality depends on which structure is affected. 

3. Complete Monocular Visual Loss Complete loss of vision in one eye can occur with severe damage to the ipsilateral optic nerve. A complete optic nerve transection therefore causes: Complete blindness of the affected eye. For example: Right optic nerve transection → complete right monocular blindness. The opposite eye remains unaffected if the lesion is confined to the right optic nerve. 

4. Other Causes of Severe Monocular Visual Loss Although optic nerve transection is the classic anatomical example, complete or profound monocular visual loss can also result from severe ocular, retinal, or optic nerve disease. Important possibilities include: Central retinal artery occlusion. Severe optic neuropathy. Retinal detachment involving the macula. Major ocular trauma. Therefore, monocular blindness does not automatically mean that the optic nerve has literally been transected. 

5. Central Scotoma A scotoma is a localized area of reduced or absent vision surrounded by relatively preserved vision. A central scotoma affects the central part of the visual field and may be experienced as a blurred, dark, or missing area directly in front of the patient. Central scotomas are particularly associated with diseases affecting the optic nerve or macula. 

6. Optic Neuritis Optic neuritis is an important cause of a central or centrocaecal scotoma. Typical features include: Reduced visual acuity. Central visual-field loss. Reduced colour vision, particularly red desaturation. Pain on eye movement. Relative afferent pupillary defect when unilateral or asymmetric. Optic neuritis is particularly associated with demyelinating disorders such as multiple sclerosis. 

7. Constricted Visual Field A constricted visual field means that the peripheral visual field progressively narrows while central vision may initially remain relatively preserved. This may eventually produce tunnel vision. Important causes include: Chronic glaucoma. Chronic papilloedema with secondary optic nerve damage. Another important cause of progressive peripheral field constriction is retinitis pigmentosa. 

8. Chronic Glaucoma In chronic glaucoma, progressive optic nerve damage produces characteristic visual-field abnormalities. Early defects may include: Paracentral scotomas. Nasal steps. Arcuate scotomas. As disease becomes advanced, the remaining visual field may become markedly constricted, producing: Tunnel vision. Therefore: Advanced chronic glaucoma → severe peripheral field constriction. 

9. Chronic Papilloedema Long-standing papilloedema from raised intracranial pressure can eventually damage optic nerve axons. Early papilloedema often causes an enlarged blind spot, while visual acuity may initially remain relatively preserved. If papilloedema persists: Chronic disc swelling → optic nerve damage → secondary optic atrophy → progressive visual-field loss. Advanced disease can therefore produce substantial field constriction and permanent visual impairment. 

10. Lesions Affecting Both Eyes When a lesion affects corresponding parts of the visual fields of both eyes, pathology at the optic chiasm or behind the chiasm should be considered. Important sites include: Optic chiasm. Optic tract. Lateral geniculate nucleus. Optic radiations. Occipital visual cortex. The exact field defect helps localise the lesion. 

11. Bitemporal Hemianopia Bitemporal hemianopia means loss of the temporal half of the visual field in both eyes. This pattern strongly suggests a lesion involving the optic chiasm. Therefore: Bitemporal hemianopia → think optic chiasm. 

12. Why Chiasmal Lesions Cause Bitemporal Hemianopia The nasal retinal fibres cross at the optic chiasm. These nasal retinal fibres carry information from the temporal visual fields. Compression of the central optic chiasm therefore preferentially damages the crossing nasal fibres. The result is: Loss of temporal visual field in both eyes → bitemporal hemianopia. 

13. Causes of Chiasmal Lesions Important causes include: Pituitary adenoma. Craniopharyngioma. Meningioma. Intracranial aneurysm, depending on its location. Other suprasellar masses may also compress the optic chiasm. 

14. Pituitary Adenoma A pituitary adenoma is a classic cause of bitemporal hemianopia. The pituitary gland lies beneath the optic chiasm. As a pituitary tumour expands upward from the sella turcica, it may compress the inferior aspect of the optic chiasm. Therefore: Pituitary mass → optic chiasm compression → bitemporal visual-field loss. Endocrine abnormalities may coexist depending on whether the tumour secretes hormones or interferes with normal pituitary function. 

15. Craniopharyngioma Craniopharyngiomas are tumours arising in the sellar or suprasellar region. Because of their proximity to the optic chiasm, they can cause: Visual-field defects. Reduced visual acuity. Endocrine abnormalities. Symptoms of raised intracranial pressure, particularly with larger lesions. Bitemporal hemianopia may occur from chiasmal compression. 

16. Homonymous Visual-Field Defects A homonymous visual-field defect affects the same side of the visual field in both eyes. For example: Right homonymous hemianopia → loss of the right visual field of both eyes. This indicates a lesion behind the optic chiasm on the opposite side. Therefore: Right homonymous field loss → left retrochiasmal lesion. Left homonymous field loss → right retrochiasmal lesion. 

17. Homonymous Quadrantanopia A homonymous quadrantanopia means loss of the same quarter of the visual field in both eyes. This commonly results from a lesion involving part of the optic radiations. The two important patterns are: Superior quadrantanopia → temporal lobe lesion. Inferior quadrantanopia → parietal lobe lesion. 

18. Superior Homonymous Quadrantanopia Fibres carrying information from the superior visual field travel through the inferior optic radiations, which loop anteriorly through the temporal lobe. This loop is known as Meyer’s loop. A temporal lobe lesion therefore produces a contralateral superior homonymous quadrantanopia. A useful memory phrase is: Temporal lesion → “pie in the sky.” For example: Left temporal lobe lesion → right superior homonymous quadrantanopia. 

19. Inferior Homonymous Quadrantanopia Fibres carrying the inferior visual field travel more superiorly through the parietal lobe. A parietal optic-radiation lesion therefore causes: Contralateral inferior homonymous quadrantanopia. A useful memory phrase is: Parietal lesion → “pie on the floor.” For example: Left parietal lesion → right inferior homonymous quadrantanopia. 

20. Homonymous Hemianopia Homonymous hemianopia means loss of the same half of the visual field in both eyes. It results from a retrochiasmal lesion. Possible sites include: Optic tract. Lateral geniculate nucleus. Optic radiations. Occipital cortex. 

21. Optic Tract Lesion An optic tract lesion produces a contralateral homonymous hemianopia. The defect is often relatively incongruous, meaning that the field defects in the two eyes are not exactly identical in shape or extent. For example: Left optic tract lesion → right homonymous hemianopia. 

22. Congruity and Lesion Location As lesions occur farther posteriorly along the visual pathway, homonymous field defects generally become more congruous. Congruous means that the field defects in the two eyes closely resemble each other. Therefore, as a general rule: Anterior retrochiasmal lesion → more incongruous. Posterior retrochiasmal lesion → more congruous. This is a useful localisation principle rather than an absolute rule. 

23. Lateral Geniculate Lesions The lateral geniculate nucleus/body is a relay station between the optic tract and optic radiations. Lesions here can cause a contralateral homonymous visual-field defect, sometimes with characteristic sectoral patterns depending on vascular anatomy. The original note associates a congruous homonymous hemianopia with a lateral geniculate lesion, but congruity alone does not precisely localise the lesion. 

24. Occipital Cortex Lesions The final part of the visual pathway is the primary visual cortex in the occipital lobe. An occipital cortex lesion typically causes a highly congruous contralateral homonymous hemianopia. One particularly important feature is: Macular sparing. 

25. Macular Sparing Macular sparing means that central vision is preserved despite loss of the surrounding homonymous visual field. This is classically associated with an occipital cortex lesion, particularly an occipital infarction. One explanation is that the occipital pole representing central vision may have overlapping vascular supply, although the mechanism is more complex than a simple fixed dual blood supply in every patient. Therefore: Homonymous hemianopia + macular sparing → strongly suggests occipital cortex involvement. 

26. Visual Field Defects – Note Form Complete monocular visual loss: severe ipsilateral retinal or optic nerve lesion; complete optic nerve transection is the classic anatomical example. 

Central scotoma: optic nerve or macular disease; optic neuritis is an important cause. 

Constricted visual field: chronic glaucoma, chronic papilloedema with optic nerve damage, or retinitis pigmentosa. 

Bitemporal hemianopia: optic chiasm lesion. 

Chiasmal causes: pituitary adenoma, craniopharyngioma, meningioma and other suprasellar masses; some aneurysms may also compress the chiasm. 

Superior homonymous quadrantanopia: contralateral temporal lobe/Meyer’s loop lesion. 

Inferior homonymous quadrantanopia: contralateral parietal optic-radiation lesion. 

Homonymous hemianopia: contralateral lesion behind the optic chiasm. 

Incongruous homonymous hemianopia: suggests a relatively anterior retrochiasmal lesion, such as the optic tract. 

Increasingly congruous field defects: generally suggest progressively more posterior lesions. 

Homonymous hemianopia with macular sparing: classically suggests an occipital cortex lesion. 

27. Easy Localisation Sequence Think of the visual pathway from front to back: One eye only → retina or optic nerve. 

Temporal fields of both eyes lost → optic chiasm. 

Same side of visual field lost in both eyes → opposite retrochiasmal pathway. 

Superior quadrant lost → opposite temporal lobe. 

Inferior quadrant lost → opposite parietal lobe. 

Very congruous homonymous hemianopia ± macular sparing → opposite occipital cortex. 

Key Clinical Pattern The most useful rule is: PRE-CHIASM → ONE EYE. CHIASM → BITEMPORAL HEMIANOPIA. POST-CHIASM → CONTRALATERAL HOMONYMOUS FIELD LOSS. For the optic radiations: Temporal lobe → superior quadrantanopia → “pie in the sky.” Parietal lobe → inferior quadrantanopia → “pie on the floor.” And finally: Occipital cortex → highly congruous homonymous hemianopia, often with macular sparing.

Medicine – Pupils, Pupillary Light Reflex, Miosis, Horner Syndrome and Mydriasis

The pupil regulates the amount of light entering the eye. Its size is controlled by opposing parasympathetic pupilloconstrictor fibres and sympathetic pupillodilator fibres.

Abnormal pupil size or reactivity can therefore help localise lesions involving the optic nerve, midbrain, oculomotor nerve, sympathetic pathway, iris, or autonomic nervous system.

An asterisk (*) signifies a common cause.

⸻

1. Parasympathetic Pupilloconstrictor Fibres

Parasympathetic fibres cause constriction of the pupil, or miosis.

The pathway begins in the Edinger–Westphal nucleus of the midbrain.

Preganglionic parasympathetic fibres then travel with the oculomotor nerve, CN III, to the ciliary ganglion in the orbit.

Postganglionic fibres travel through the short ciliary nerves to the:

Sphincter pupillae → constricts the pupil.

Ciliary muscle → allows accommodation for near vision.

Therefore:

Parasympathetic activation → miosis + accommodation.

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2. Sympathetic Pupillodilator Fibres

Sympathetic fibres cause dilatation of the pupil, or mydriasis.

The pathway begins in the hypothalamus and descends through the brainstem to the ciliospinal centre of Budge, approximately at spinal cord levels C8–T2.

Preganglionic fibres then leave the spinal cord, pass through the sympathetic chain, and ascend to the superior cervical ganglion.

Postganglionic fibres accompany the internal carotid artery into the skull and ultimately reach the eye.

They supply the:

Dilator pupillae → pupil dilatation.

They also contribute to eyelid elevation through Müller’s superior tarsal muscle and supply sympathetic fibres involved in facial sweating.

⸻

3. Pupillary Light Reflex

The pupillary light reflex is the constriction of the pupils in response to light.

Shining light into one eye normally produces:

Direct response → constriction of the illuminated pupil.

Consensual response → constriction of the opposite pupil.

This occurs because the central pathway projects bilaterally to the Edinger–Westphal nuclei.

⸻

4. Afferent Limb of the Light Reflex

The afferent limb detects the incoming light stimulus.

The pathway is:

Retina → optic nerve (CN II) → optic chiasm/optic tract → pretectal nuclei of the midbrain.

An important correction to the original note is that the lateral geniculate body is not the principal relay of the pupillary light reflex.

The lateral geniculate nucleus is primarily part of the pathway responsible for conscious vision.

For the pupillary reflex, fibres leave the optic tract and synapse in the pretectal area of the midbrain.

⸻

5. Bilateral Midbrain Connection

Each pretectal nucleus sends fibres to both Edinger–Westphal nuclei.

This bilateral connection explains why shining light in one eye normally constricts both pupils.

Therefore:

One retina stimulated → both Edinger–Westphal nuclei activated → both pupils constrict.

⸻

6. Efferent Limb of the Light Reflex

The efferent limb is parasympathetic.

The pathway is:

Edinger–Westphal nucleus → CN III → ciliary ganglion → short ciliary nerves → sphincter pupillae → pupillary constriction.

Therefore:

Afferent limb = CN II.

Efferent limb = CN III parasympathetic fibres.

⸻

7. Pupillary Light Reflex – Note Form

Light enters eye → retina.

⸻

Retina → optic nerve, CN II.

⸻

Optic nerve fibres → optic chiasm and optic tract.

⸻

Fibres leave visual pathway → pretectal nuclei in midbrain.

⸻

Pretectal nuclei → bilateral Edinger–Westphal nuclei.

⸻

Edinger–Westphal nucleus → CN III.

⸻

CN III → ciliary ganglion.

⸻

Short ciliary nerves → sphincter pupillae.

⸻

Result → direct and consensual pupillary constriction.

⸻

8. Causes of a Small Pupil – Miosis

Miosis means abnormal or marked constriction of the pupil.

Important causes include:

Age-related or senile miosis.

Horner syndrome.

Argyll Robertson pupil.

Certain autonomic disorders.

Opiates.

Pilocarpine and other miotic drugs.

⸻

9. Senile Miosis

Pupils tend to become smaller with increasing age.

This physiological age-related reduction in pupil diameter is sometimes called senile miosis.

It is generally bilateral and does not itself indicate neurological disease.

⸻

10. Horner Syndrome

Horner syndrome results from interruption of the sympathetic pathway supplying the eye and face.

The classic features are:

Ptosis.

Miosis.

Anhidrosis, depending on the level of the lesion.

A traditional fourth feature is enophthalmos, although the eye is usually not truly displaced backward.

⸻

11. Miosis in Horner Syndrome

The sympathetic system normally activates the dilator pupillae muscle.

Loss of sympathetic input means the affected pupil cannot dilate normally.

Parasympathetic constrictor activity is therefore relatively unopposed.

The result is:

Ipsilateral miosis.

The difference in pupil size, or anisocoria, becomes more obvious in the dark because the abnormal pupil fails to dilate properly.

Therefore:

Horner anisocoria → greater in darkness.

⸻

12. Ptosis in Horner Syndrome

The sympathetic fibres supply Müller’s superior tarsal muscle, which contributes a small amount to upper-eyelid elevation.

Loss of this sympathetic supply causes a mild ptosis.

This differs from third nerve palsy, where paralysis of the levator palpebrae superioris may cause much more severe ptosis.

Therefore:

Horner → mild ptosis.

CN III palsy → often marked ptosis.

⸻

13. Anhidrosis

Anhidrosis means reduced or absent sweating.

Its distribution depends on where along the sympathetic pathway the lesion occurs.

Central or preganglionic lesions are more likely to cause significant facial anhidrosis.

Postganglionic lesions associated with the internal carotid artery may produce little or no facial anhidrosis because many sweat fibres have already travelled with the external carotid circulation.

⸻

14. Enophthalmos

Traditional descriptions of Horner syndrome include enophthalmos, meaning that the eye appears sunken.

In humans this is usually apparent rather than true enophthalmos.

The combination of mild upper-lid ptosis and slight elevation of the lower eyelid makes the palpebral opening smaller, giving the impression that the eye lies deeper in the orbit.

⸻

15. The Three-Neurone Sympathetic Pathway

The sympathetic pathway involved in Horner syndrome can be divided into:

First-order central neurone.

Second-order preganglionic neurone.

Third-order postganglionic neurone.

The site of interruption helps determine the possible underlying cause.

⸻

16. First-Order or Central Horner Syndrome

First-order fibres descend from the hypothalamus through the brainstem and cervical spinal cord.

Important causes include:

*Brainstem stroke or other vascular lesion. **

Tumour.

Demyelination, including multiple sclerosis.

Spinal cord lesions.

Other neurological findings are often present because central lesions usually involve neighbouring structures.

⸻

17. Vascular Causes*

A brainstem vascular lesion, particularly a lateral medullary stroke, can interrupt descending sympathetic fibres and cause Horner syndrome.

The patient may also have other brainstem signs, such as:

Vertigo.

Ataxia.

Dysphagia.

Sensory abnormalities.

Therefore, Horner syndrome accompanied by other acute neurological deficits should raise concern for a central vascular lesion.

⸻

18. Preganglionic Horner Syndrome

Second-order sympathetic fibres leave the spinal cord and travel through the upper chest and neck before reaching the superior cervical ganglion.

Because this pathway passes close to the lung apex, lesions in the chest can produce Horner syndrome.

⸻

19. Pancoast Tumour*

A Pancoast tumour, or superior sulcus lung tumour, is an important cause of preganglionic Horner syndrome.

The tumour occurs near the lung apex and may invade the sympathetic chain.

It may produce:

Horner syndrome.

Shoulder or arm pain.

Brachial plexus involvement.

Therefore:

Horner syndrome + shoulder/arm pain → consider an apical lung tumour.

⸻

20. Other Chest Causes

Other lesions affecting the sympathetic chain in the thoracic inlet or mediastinum can also cause Horner syndrome.

These include:

Mediastinal masses.

Other apical thoracic lesions.

A cervical rib was traditionally listed as a possible cause through local compression, although it is much less important clinically than malignant or traumatic causes.

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21. Cervical Causes

The sympathetic chain passes through the neck, where it may be damaged by:

Cervical lymphadenopathy.

Neck trauma.

Thyroid or other cervical tumours.

Therefore, neck examination is important in unexplained Horner syndrome.

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22. Surgical and Iatrogenic Causes*

Horner syndrome can occur following procedures involving the neck.

Examples include:

Thyroid surgery.

Carotid surgery, including carotid endarterectomy.

Other cervical or thoracic operations.

Modern arterial catheter procedures can also occasionally damage the sympathetic pathway, although older references to carotid angiography as a common cause reflect historical practice.

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23. Postganglionic Horner Syndrome

Third-order sympathetic fibres leave the superior cervical ganglion and accompany the internal carotid artery toward the skull.

Important causes include:

Internal carotid artery dissection.

Cavernous sinus disease.

Other lesions along the internal carotid sympathetic plexus.

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24. Internal Carotid Artery Dissection

Internal carotid artery dissection is an especially important cause of acute painful Horner syndrome.

The sympathetic fibres run along the wall of the internal carotid artery and may be damaged when the artery dissects.

A classic presentation is:

Acute unilateral Horner syndrome + ipsilateral neck, facial, or head pain.

This requires urgent assessment because carotid dissection can cause cerebral ischaemia and stroke.

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25. Cavernous Sinus Lesion

Sympathetic fibres travel through the cavernous sinus alongside several cranial nerves.

A cavernous sinus lesion may therefore produce Horner syndrome together with:

Diplopia.

Ophthalmoplegia.

Trigeminal sensory abnormalities.

Other cranial nerve deficits.

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26. Horner Syndrome – Note Form

Sympathetic lesion → Horner syndrome.

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Miosis → loss of pupillary dilator activity.

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Ptosis → loss of sympathetic supply to Müller muscle.

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Anhidrosis → distribution depends on lesion level.

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Apparent enophthalmos → narrowing of palpebral fissure rather than true posterior displacement.

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Central causes: stroke, tumour, demyelination and spinal cord lesions.

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Preganglionic causes: Pancoast tumour, thoracic/mediastinal lesions, neck tumour or trauma, thyroid or carotid surgery.

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Postganglionic causes: internal carotid artery dissection and cavernous sinus lesions.

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27. Argyll Robertson Pupil

The Argyll Robertson pupil is classically a small, irregular pupil that accommodates but does not react normally to light.

This phenomenon is called:

Light-near dissociation.

In simple terms:

No or poor light response.

Near/accommodation response preserved.

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28. Association of Argyll Robertson Pupil

Argyll Robertson pupils are classically associated with neurosyphilis, particularly late syphilitic neurological disease.

The traditional memory phrase is:

“Accommodates but does not react.”

The finding is much less common in modern clinical practice than older textbooks suggest.

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29. Myotonic Dystrophy

Pupillary abnormalities can occur in myotonic dystrophy, including relatively small pupils and impaired pupillary responses.

However, miosis is not usually the key diagnostic feature.

More characteristic findings include:

Myotonia.

Distal muscle weakness.

Facial and temporal muscle wasting.

Early cataracts.

Cardiac conduction disease.

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30. Opiates

Opiates or opioids commonly cause bilateral marked pupillary constriction.

The classic description is:

Pinpoint pupils.

In opioid toxicity, this may occur with:

Reduced level of consciousness.

Respiratory depression.

Therefore:

Coma + respiratory depression + pinpoint pupils → strongly consider opioid toxicity, while remembering that other causes of coma can sometimes alter pupils as well.

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31. Pilocarpine

Pilocarpine is a muscarinic cholinergic agonist.

It stimulates the sphincter pupillae and causes:

Miosis.

It has ophthalmic uses, although its role in modern glaucoma treatment is more limited than historically.

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32. Causes of a Large Pupil – Mydriasis

Mydriasis means dilatation of the pupil.

It may result from:

Loss of parasympathetic constrictor activity.

or

Excess sympathetic activity/pharmacological stimulation.

Important causes include:

Adie tonic pupil.

Third nerve palsy.

Drugs.

Trauma.

Previous eye surgery.

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33. Adie Tonic Pupil

An Adie tonic pupil usually results from damage to parasympathetic fibres in or after the ciliary ganglion.

It typically produces a pupil that is:

Dilated.

Poorly reactive to light.

Slow or tonic in its response to near stimulation and redilatation.

The near response is often better preserved than the light response, producing another form of light-near dissociation.

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34. Holmes–Adie Syndrome

When the tonic pupil is associated with reduced or absent deep tendon reflexes, the condition is called Holmes–Adie syndrome.

Therefore:

Adie pupil + reduced tendon reflexes = Holmes–Adie syndrome.

It commonly affects otherwise healthy younger adults and is usually benign.

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35. Third Nerve Palsy

The third cranial nerve carries parasympathetic fibres responsible for pupil constriction.

Damage to these fibres may therefore result in:

Dilated pupil.

Poor or absent light reaction.

If a large pupil occurs together with:

Ptosis.

Down-and-out eye.

Diplopia.

a third nerve palsy should be suspected.

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36. Aneurysm and a Dilated Pupil

A particularly important emergency is:

Painful third nerve palsy + dilated pupil.

This raises concern for compression by a posterior communicating artery aneurysm.

Therefore, a new pupil-involving third nerve palsy requires urgent assessment.

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37. Drugs Causing Mydriasis

Many drugs can cause pupillary dilatation.

Important examples include:

Atropine.

Tropicamide.

Sympathomimetic/stimulant drugs such as amphetamines.

Some antidepressants and other medications with anticholinergic effects.

Atropine and tropicamide cause mydriasis mainly by blocking parasympathetic muscarinic activity at the iris sphincter.

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38. Tropicamide

Tropicamide is a short-acting antimuscarinic drug commonly used during ophthalmic examination to dilate the pupil.

It produces:

Mydriasis.

and some degree of:

Cycloplegia, or reduced accommodation.

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39. Atropine

Atropine blocks muscarinic receptors.

In the eye it causes:

Mydriasis.

Cycloplegia.

Its ocular effects last considerably longer than those of tropicamide.

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40. Trauma and Previous Eye Surgery

Direct trauma to the iris sphincter can leave the pupil abnormally dilated or irregular.

This is sometimes called traumatic mydriasis.

Previous ophthalmic surgery may also alter the shape, size or reactivity of the pupil.

Therefore, examination for:

Iris injury.

Surgical scars.

An irregular pupil.

may help identify a local ocular cause.

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41. Small Pupil – Note Form

Senile miosis: physiological pupil narrowing with age.

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Horner syndrome: miosis + mild ptosis ± anhidrosis.

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Argyll Robertson pupil: small irregular pupil with light-near dissociation; classically neurosyphilis.

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Opiates: bilateral pinpoint pupils, particularly important in opioid toxicity.

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Pilocarpine: pharmacological muscarinic stimulation causing miosis.

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42. Large Pupil – Note Form

Adie tonic pupil: large pupil with poor light response and tonic near response.

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Holmes–Adie syndrome: Adie pupil + reduced/absent tendon reflexes.

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Third nerve palsy: dilated pupil ± ptosis and down-and-out eye.

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Atropine/tropicamide: antimuscarinic pupillary dilatation.

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Amphetamines and other sympathomimetics: may cause mydriasis.

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Trauma/surgery: damage to iris sphincter may cause a persistently large or irregular pupil.

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43. Horner versus Third Nerve Palsy – Note Form

Horner syndrome → pupil SMALL.

Third nerve palsy → pupil may be LARGE.

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Horner ptosis → mild.

Third nerve ptosis → often marked.

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Horner eye movements → usually normal.

Third nerve palsy → eye movements markedly abnormal.

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Horner eye position → no classic down-and-out deviation.

Third nerve palsy → down-and-out eye.

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Horner anisocoria → greater in the DARK.

Parasympathetic pupil palsy → anisocoria usually greater in BRIGHT light because the large abnormal pupil cannot constrict.

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Key Clinical Pattern

The easiest way to organise pupillary abnormalities is to ask which autonomic pathway has failed.

Parasympathetic fibres constrict the pupil.

Sympathetic fibres dilate the pupil.

Therefore:

Sympathetic failure → small pupil → Horner syndrome.

Parasympathetic failure → large pupil → third nerve palsy, Adie pupil or antimuscarinic drug effect.

For the light reflex remember:

CN II IN → midbrain → bilateral Edinger–Westphal nuclei → CN III OUT.

And the most important emergency patterns are:

Painful Horner syndrome → consider internal carotid artery dissection.

Painful third nerve palsy with a dilated pupil → urgently exclude posterior communicating artery aneurysm.