THE RAMSAY HUNT SYNDROME (PROGRESSIVE MYOCLONIC ATAXIA)

Causes of progressive myoclonic ataxia include:

1  Unverricht-Lundborg disease (Baltic or Mediterranean myoclonus) is an autosomal recessive early onset spinocerebellar degeneration (see above under Early onset metabolic ataxias). The onset is in childhood with seizures and myoclonus, while ataxia and mild cognitive impairment appear later. The condition is caused by mutations of the cystatin B (EPM1A) gene on chromosome 21q22.3. There is another gene - EPM1B - on chromosome 12. EPM1A may account for a high proportion of unexplained myoclonus cases.

2  Lafora body disease is also an autosomal recessive disorder with onset in adolescence and severe epilepsy and dementia with milder myoclonus. A milder later onset form exists. Characteristic periodic acid Schiff-positive inclusions are seen in skin, muscle, brain and liver. Various mutations of the EPM2A gene on chromosome 6q24 have been identified; the function of the gene product, laforin, is unknown. Other genes can also cause Lafora body disease (malin (NHLRC1) and another gene referred to as EPM2B).

3  Neuronal ceroid lipofuscinosis can occur at various ages, with combinations of epilepsy, myoclonus, visual failure and ataxia. Characteristic inclusions are seen in neurones (detectable in rectal or skin biopsies). Inheritance can be autosomal recessive or dominant. An axillary skin biopsy can detect ceroid lipofuscinosis or Lafora bodies.

Sialidosis is inherited as an autosomal recessive disorder, caused by a-N-acetylneuraminidase (sialidase) deficiency. The onset is in adolescence or early adult life with epilepsy, myoclonus, visual failure (with cherry red maculae) and ataxia. Various mutations of the sialidase NEU1 gene on chromosome 6p21 have been detected. Diagnosis is by measurement of urinary sialyloligosaccharides or neuraminidase levels.

Mitochondrial disease takes many forms including the MERRF syndrome (myoclonic epilepsy with ragged red fibres). The ragged red fibres are a muscle biopsy feature caused by an accumulation of abnormal mitochondria. In addition to myoclonic ataxia, there is often smallness of stature, deafness, dementia and sometimes subcutaneous lipomas. The majority of MERRF cases are caused by a point mutation of the mitochondrial lysine transfer RNA gene (at position 8344). A few cases have been associated with other mutations of mitochondrial DNA (at positions 8356 and 3243) and, in some, the molecular basis has not been determined. Dentatorubropallidoluysian atrophy is described below. A Ramsay Hunt phenotype may occur.

Coeliac disease may be associated with a cerebellar ataxia with myoclonus or other neurological complications including cerebral calcification, seizures, peripheral neuropathy or a Friedreich’s ataxia-like illness. Diagnosis is by antibodies (to gliadin or endomysial) or small bowel biopsy. The neurological disorder does not respond to a gluten-free diet. Whipple's disease is associated with several neurological complications, including focal brain lesions, ataxia (with myoclonus), supranuclear eye movement abnormalities and dementia. Myoclonus may affect the eyes and face (oculomasticatory myorhythmia). Biopsy of the small bowel or detection of the organism Tropheryma whippelii directly or by polymerase chain reaction (PCR) analysis of DNA in bowel or CSF may allow the diagnosis. Treatment is with antibiotics.

Creutzfeldt-Jakob disease classically presents with rapidly progressive cerebellar ataxia and myoclonus, as well as dementia and sometimes cortical visual disturbances. A familial

Paraneoplastic cerebellar degeneration is a rare disorder most commonly seen in association with small cell lung cancer, ovarian or uterine cancer or lymphoma and may precede the appearance of the tumour.

Severe ataxia develops rapidly, over weeks or months, along with dysarthria, vertigo, oscil-lopsia and nystagmus. The condition then stabilizes, but the patients are severely disabled. It is the severe subacute onset and rapid deterioration that is characteristic of paraneoplastic ataxia. Other paraneoplastic disorders, such as Lambert-Eaton syndrome, opsoclonus, peripheral neuropathy or limbic encephalitis often coexist with the cerebellar syndrome.


(autosomal dominant) form, Gerstmann-Straussler-Scheinker (GSS) disease, causes a prominent ataxic presentation followed by more typical dementia and myoclonus.

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