Wolfram Syndrome Guide for Neurologists
In Wolfram Syndrome nearly every organ/body system may be affected. Characteristic changes in the central nervous system occur beginning at a very early age. Wolfram Syndrome is typically associated with sensorineural hearing loss and other progressive neurological abnormalities. The natural history of Wolfram Syndrome was described in 45 individuals studied (mean age 16 years, range 5-32 years) from 29 families in the UK (Barrett et al 1995). Hearing impairment was present in 64%. Sixty percent of all individuals had one or more of the following signs and/or symptoms: ataxia, peripheral neuropathy, cognitive impairment, early onset dementia (disinhibition and/or short term memory loss), psychiatric illness (most commonly depression), and central sleep apnea. MRI scans in individuals with this syndrome may show generalised brain atrophy with loss of the posterior pituitary bright spot, thinning of the optic nerves, and loss of volume of the cerebellum and brainstem.
Suggested evaluation of neurologic manifestations:
Management through multidisciplinary team input and rehabilitation including:
Suggested evaluation of neurologic manifestations:
- Annual neurological examination for asymptomatic patients and bi-annually for symptomatic patients
- Brain MRI scan at diagnosis and to be repeated if acute deterioration of neurological signs and/or symptoms or at adult age
- Cerebellar ataxia assessment:
- - Use of validated ataxia-specific rating scales for measuring progression : SARA (see supplementary data)
- - Washington unified rating scale (WURS)
- Peripheral neuropathy assessment:
- Presence of symptoms such as numbness, tingling, burning, jabbing or electric-like pain or absence of deep tendon reflexes
- Presence of signs and / or symptoms of cardiovascular and / or gastrointestinal autonomic neuropathy
- Nerve conduction studies, Tilt-test in presence of autonomic cardiovascular symptoms, other investigations as per advice of cardiology and / or gastroenterology specialists
- Brainstem (respiratory drive) involvement assessment:
- Screening by polysomnography or nocturnal oximetry (every 2 years)
- Epilepsy assessment:
- Electroencephalography if seizures occur
- Cognitive/Psychiatric assessment:
- Neuropsychological testing adapted to age (Children: WISC-IV; Adult: MMSE, FAB) and to vision difficulties
- Mental health assessment:
- Assessment includes taking a complete history and performing a detailed examination. Consider patient’s appearance, behaviour, speech, mood, thinking and any abnormal perceptions
- Screening for anxiety, depression, abnormal behaviour (obsessive-compulsive behaviours, aggression, eating disorders etc.) or psychosis
Management through multidisciplinary team input and rehabilitation including:
- Ophthalmology services and visual impairment team input to optimise visual functioning
- Physiotherapy and occupational therapy team input with regards physical (gross motor and
fine motor / coordination) difficulties - Speech and language therapy input with regards dysarthria (speech difficulties) and
swallowing difficulties (which may lead to recurrent chest infections due to aspiration) - Drug treatments for spasticity (oral anti-spasticity medications such as baclofen, and/or
botulinum toxin injections) - If neuropathic pain is present consider starting treatment for this – eg. Gabapentin, Pregablin, Carbamazepine, Amitriptyline, Lidocaine patch and / or transcutaneous electrical nerve stimulation (TENS)
- Anti-epileptic drugs and counseling if seizures occur
- Consider referral for expert mental health care
- Peripheral neuropathy assessment:
- Presence of symptoms such as numbness, tingling, burning, jabbing or electric-like pain or absence of deep tendon reflexes
- Presence of signs and / or symptoms of cardiovascular and / or gastrointestinal autonomic neuropathy
- Nerve conduction studies, Tilt-test in presence of autonomic cardiovascular symptoms, other investigations as per advice of cardiology and / or gastroenterology specialists