Anti-ganglioside antibodies in idiopathic and hereditary cerebellar degeneration

Cerebellar degeneration has been associated with gluten sensitivity and celiac disease. Patients with celiac disease may have neuropathy and antibodies to gangliosides. The authors investigated the presence of antiganglioside antibodies in 22 patients with hereditary and nonhereditary ataxia and found 64% reactive in a novel agglutination test.     

Internuclear ophthalmoplegia and cerebellar ataxia: report of one case.

Deep hemispheric or brainstem small infarcts can lead to atypical lacunar syndromes. Unilateral internuclear ophthalmoplegia (INO) and cerebellar ataxia has not been reported previously. A 57-year-old hypertensive female presented with bilateral appendicular and left truncal cerebellar ataxia and right INO. Cranial MRI showed a right paramedian infarct of lacunar size located in the tegmentum of caudal mesencephalon. At this level the involvement of medial longitudinal fascicle (MLF) led to right INO and the lesion of brachium conjunctivum caused the bilateral cerebellar ataxia. Ipsilateral involvement of both cerebellofugal fibers, before and after decussation, was responsible for bilateral cerebellar ataxia.     

Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia. A unique and partially treatable clinico-pathological entity

A family with a dominant form of neuronal degeneration, marked clinically by ataxia, hyperreflexia, distal motor weakness, extrapyramidal rigidity, bulbar signs, and ophthalmoplegia has been followed for some years. Recent post-mortem study of 1 member revealed degeneration of the anterior horn cells, spino-cerebellar tracts, pons, dentate nucleus, substantia nigra, and oculomotor nuclei. This pattern of involvement appears to be a unique variant of neuronal degeneration, sharing features of both spino-cerebellar and extra-pyramidal system degenerations. Furthermore, the extrapyramidal signs of 3 affected family members have responded to a combination of dopaminergic and central anti-cholinergic medications; levodopa, amantidine hydrochloride, and trihexyphenidyl hydrochloride.     

Familial form of cutaneous epitheliomatosis with complex neurological characteristics similar to hereditary spinocerebellar degeneration. Apropos of 4 cases including one case with anatomo-clinical description]

The authors report an observation in which four siblings were affected by both multiple cutaneous epitheliomatosis and complex but relatively stereotyped neurological disorders. Clinically, the main syndrome was cerebello-spinal ataxia with involvement of the anterior horns of the spinal cord with less marked pyramidal and extra-pyramidal features. Neuropathological examination of one of the cases revealed lesions of essentially cerebello-spinal degeneration suggestive of Menzel's disease. The possible connection between the neural and cutaneous lesions is discussed. All the various etiological categories possible have been ruled out; not one being entirely satisfactory, except for the very broad category of genetic neuro-dermatoses.     

Hereditary cerebellar degeneration with downbeat nystagmus. A case and it''s treatment

We present a female patient of 48 years with downbeat nystagmus (DBN), moderate impairment of coordination testing and a family history of cerebellar ataxia. We report that a single 2 mg dose of clonazepam (following Currie & Matsuo) resulted in a virtual disappearance of nystagmus and of the patient's symptom of oscillopsia. This result is interpreted in terms of current models of DBN.     

Progressive spinal axonal degeneration and slowness in ALS2-deficient mice

OBJECTIVE: Homozygous mutation in the ALS2 gene and the resulting loss of the guanine exchange factor activity of the ALS2 protein is causative for autosomal recessive early-onset motor neuron disease that is thought to predominantly affect upper motor neurons. The goal of this study was to elucidate how the motor system is affected by the deletion of ALS2. METHODS: ALS2-deficient mice were generated by gene targeting. Motor function and upper and lower motor neuron pathology were examined in ALS2-deficient mice and in mutant superoxide dismutase 1 (SOD1) mice that develop ALS-like disease from expression of an ALS-linked mutation in SOD1. RESULTS: ALS2-deficient mice demonstrated progressive axonal degeneration in the lateral spinal cord that is also prominent in mutant SOD1 mice. Despite the vulnerability of these spinal axons, lower motor neurons in ALS2-deficient mice were preserved. Behavioral studies demonstrated slowed movement without muscle weakness in ALS2(-/-) mice, consistent with upper motor neuron defects that lead to spasticity in humans. INTERPRETATION: The combined evidence from mice and humans shows that deficiency in ALS2 causes an upper motor neuron disease that in humans closely resembles a severe form of hereditary spastic paralysis, and that is quite distinct from amyotrophic lateral sclerosis.     

An unusual association of dentato-rubral degeneration with spinal ataxia,ophthalmoplegia and multiple cranial nerve palsies

Summary Clinical and neuropathological data of a 50-year-old woman with an unusual multisystem degeneration are presented. Clinically the illness was characterized by progressive ataxia with ophthalmoplegia and multiple cranial nerve palsies. Neuropathological investigation showed a severe and selective degeneration of the dentato-rubral system, of the posterior columns and of several cranial nerve nuclei. The problems of differential diagnosis and classification are discussed.     

Progressive degeneration of motor nerve terminals in GAD mutant mouse with hereditary sensory axonopathy

The evolution of motor nerve degeneration was examined in gracile axonal dystrophy (GAD) mutant mice, which develop initial sensory ataxia and subsequent motor paresis. Using the anterior gracilis (AG) muscle, which is innervated at two discrete and well-separated end-plate zones, we demonstrated that axonal degeneration occurred first at motor nerve terminals in the distal end-plate zone, and then extended gradually from the distal to the more proximal parts of affected axons in the intramuscular nerve trunk. In contrast to the degeneration in the distal zone, active degeneration was less marked in the proximal endplate zone and, furthermore, most terminal axons had begun to produce regenerating sprouts. Ventral horn cells were histologically normal, even at advanced stages. These results indicate that, as previously observed in sensory nerves, dying back degeneration progresses later in the lower motor neuron system, even within one muscle. The mechanism(s) influencing the activation of axonal regeneration are discussed. This mutant mouse will be a useful model for the study of regenerating phenomena in dying back degeneration of genetically compromised motor neurons, as well as for the study of the pathogenesis of hereditary sensory and motor neuropathies in man.     

Progressive spinal muscular atrophy and parathyroid adenoma. Clinico-pathologic study of a case

A 82 year-old man died 6 years after the onset of a progressive spinal muscular atrophy. Post-mortem examination disclosed a parathyroid adenoma. Weakness and wasting were prominent in the proximal lower limbs. There were no fasciculations. Involvement of the medulla was mild and late. These clinical features were also present in 16 reported cases, which were improved by treatment of primary or secondary hyperparathyroidism. Our patient differs by the involvement of the hand muscles and the loss of tendon reflexes. Neuropathological study, as in one other reported case, showed a loss of anterior horn cells. Such cases underline that calcium metabolism must be studied in syndromes of spinal muscular atrophy.     

A case of paraneoplastic cerebellar degeneration with resting tremor]

A 65-year-old woman was operated for gastric adenocarcinoma in 1989. Six years later, peritonitis carcinomatosa, swelling of periaortic lymphnodes and high serum CA-125 were discovered. She received chemotherapy with 5-FU and cisplatin resulting in reduction of ascites. In September, 1998, the swelling of left supraclavicular lymphnodes and the elevation of serum CA-125 reappeared. Pathological diagnosis of supraclavicular lymphnodes was adenocarcinoma. Serum CA-125 was normalized by chemotherapy using cisplatin, farumorubicin and endoxan. However, unsteadiness appeared since December 10, 1998 followed by dysarthria and involuntary movement of neck and upper limbs. These symptoms progressed subacutely. The physical examination on admission revealed swelling of left suraclavicular lymphnodes, nystagmus on lateral gaze, saccadic eye movement on smooth pursuit and severe cerebellar ataxia. In addition, resting tremor of 3-4 Hz was observed at right hand, left wrist and neck which tended to increase amplitude by calculation. Similar movements were seen in the left first toe, though the frequency was lower. Brain MRI revealed mild cerebellar atrophy. She was diagnosed as paraneoplastic cerebellar degeneration (PCD) by serum anti Yo antibody and clinical course. The study of HLA showed positive link to A4 without A24. The primary focus of adenocarcinoma in cervical lymphnodes was suggested to be ovary rather than stomach due to the pattern of immunostaining for cytokeratin, CEA and CA125, although no carcinoma was found in ovarium clinically. The feature of this case is a PCD with resting tremor of frequency of 3-4 Hz and negative link to HLA-A24 in Japanese.