Patient profiles
UNIQUE CHALLENGES BY AGE OF ONSET
UNIQUE CHALLENGES BY AGE OF ONSET
Alexander disease presents differently in early-onset and adult-onset cases, often leading to distinct diagnostic considerations. The following case studies illustrate these variations and associated clinical features.
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EARLY-ONSET ALEXANDER DISEASE67
(BIRTH to 6 MONTHS)
First Symptoms
- Seizures began at 6 months
- Gradual psychomotor regression
Examination & Intervention
- Pediatric consultation
- Phenytoin prescribed
- Seizures controlled temporarily
- Inconclusive diagnosis
due to lack of diagnostic findings and financial constraints
Presenting symptoms
Motor decline
Gait and postural abnormalities
Cognitive delays
Speech loss, poor social interaction
Feeding issues
Vomiting, difficulty swallowing
Oral findings
Carious, hypoplastic posterior teeth
Examination
- No macrocephaly
- Flattened occipital region
- Hematology normal
Diagnostic workup
- Preanesthesia evaluation prompted MRI
MRI findings:
- Extensive white matter abnormalities
- Reduced white matter intensity in frontal lobes with prominent parafalcine and sulcal region
- Thinning of corpus callosum
- Frontal lobe demyelination
- Periventricular rim changes (T2 hypointensity)
ALEXANDER DISEASE
The final diagnosis was based primarily on MRI hallmark features. Genetic testing was not required for confirmation.
Key differential diagnoses considered:
- Adrenoleukodystrophy
- Canavan disease
- Brain tumors
- Metachromatic leukodystrophy
DENTAL
Teeth were extracted without any complications
Neurology
A referral was provided for cognitive and behavioral therapy
CONSIDER Alexander Disease when A PATIENT PRESENTS with:
- Seizures
- Motor decline
- Macrocephaly
(atypical cases can present with normal head size) - Cognitive delays
- Feeding issues
- Hallmark white matter changes in MRI
EARLY-ONSET ALEXANDER DISEASE68
1 YEAR to 4 YEARS
First symptoms
- Intermittent head drop movements for 5 months, beginning at age 4
- Frequency of head drop movement increased over time, occurring multiple times daily
- Atonic seizures since age 1 identified as cause of head drop movements
Examination & Intervention
- Pediatric consultation
- Sodium valproate prescribed, seizures controlled
Diagnostic Workup
- Video-encephalography (VEEG) performed
- VEEG findings: abnormal epileptiform discharges confirmed atonic seizures
Presenting symptoms
- Worsening frequency and severity of head drop episodes
- Progressive worsening prompted referral for neurological evaluation and further testing
Examination
- Neurological evaluation performed
- Findings normal
Diagnostic workup
MRI findings
Bilateral paraventricular and bilateral subfrontal cortex abnormalities; prompt referral for genetic testing
Genetic testing findings
GFAP gene mutation
(c.262 C>T, heterozygous)
ALEXANDER DISEASE
Diagnosis confirmed based on MRI and genetic test findings
Key differential diagnoses considered:
Lennox-Gastaut syndrome
Myoclonic-astatic epilepsy
Other leukodystrophies
- Sodium valproate maintained as seizure control therapy
- No further atonic seizures reported posttreatment
- Regular monitoring for potential symptom progression
Some cases of Alexander disease may present primarily with epilepsy (such as atonic seizures) without other expected neurological symptoms, like cognitive delays or motor dysfunction.
CONSIDER Alexander Disease when A PATIENT PRESENTS with:
- Atonic seizures/head drop movements
- Progressive worsening of symptoms or frequency in seizure
LATE-ONSET ALEXANDER DISEASE69
(7 YEARS PRIOR TO DIAGNOSIS)
First Symptoms
- Upper extremity paresthesias
- Gradual development of gait problems
Examination & Intervention
- Neurological consultation
- Initial diagnosis of multiple sclerosis
- Treatment initiated with disease-modifying therapies
Diagnostic Workup
- Non-specific findings leading to multiple sclerosis diagnosis
(OVER THE COURSE OF 1 YEAR)
Presenting symptoms
Weakness in limbs
Rapid worsening of weakness in all limbs
Dysphagia
Difficulty swallowing with certain liquids and foods
Ambulation issues
Complete loss of ambulation
Respiratory issues
Respiratory compromise requiring mechanical ventilation
Examination
- Physical exam:
Quadriplegia, hyperreflexia, right foot sustained clonus - Bilateral horizontal and vertical nystagmus with oscillatory component
Diagnostic workup
MRI findings
Abnormal signal intensity in paramedian thalami, hypothalamus, midbrain, pons, medulla, and central cervical, with significant medullary atrophy, cervical cord thinning down to C6
- Lumbar puncture: CSF-specific oligoclonal bands without pleocytosis
Due to unusual progression and MRI findings, subsequent genetic analysis of GFAP gene requested - Genetic testing findings: GFAP mutation (c.265T>C; p.Phe89Leu, homozygous)
ALEXANDER DISEASE
- Diagnosis confirmed based on MRI and genetic test findings
- Prior multiple sclerosis diagnosis reconsidered and ruled out
RESPIRATORY SUPPORT
Mechanical ventilation for respiratory support
Neurology
Follow-up for symptomatic management
GENETIC COUNSELING
Genetic counseling is recommended
CONSIDER Alexander Disease when A PATIENT PRESENTS with:
- Progressive neurological decline with atypical features
- Bulbar signs, quadriplegia, respiratory compromise
- Hallmark white matter changes and medullary atrophy in MRI
Resources
Visit our Resources page for information and tools to assist healthcare providers in providing optimal care to their patients with Alexander disease.