Hereditary Cerebellar Ataxia with Peripheral Neuropathy and Mental Retardation
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Abstract:
We present here 5 patients with hereditary cerebellar ataxia with peripheral neuropathy and mental retardation as determined by clinical, pathological, and molecular studies. The most characteristic features of this disorder, in contrast to Friedreich's ataxia, were early onset of ataxic gait, mental retardation, and a marked atrophy of the cerebellum. Sural nerve biopsy showed a reduction of myelinated fibers. The expansion of a GAA triplet repeat within the first intron of the frataxin gene, which causes Friedreich's ataxia, was not identified in any of the patients. Hereditary cerebellar ataxia with peripheral neuropathy and mental retardation represents a specific clinical entity that so far has only been described in Japan.Keywords:
Frataxin
Cerebellar ataxia
Gait Ataxia
Sural nerve
Addison’s disease is a common endocrinopathy often diagnosed in patients presenting with hyponatraemia. Cerebellar ataxia as a presentation of hyponatraemia is extremely rare. A 42-year-old man presented with vomiting, fever, ataxic gait and scanning type of dysarthria. Clinical examination revealed signs suggestive of isolated cerebellar involvement. Patient was found to have severe hyponatraemia and serum cortisol was found to be extremely low while MRI brain was found to be normal. Corticosteroid therapy was initiated and cerebellar ataxia was resolved following normalisation of sodium levels.
Dysarthria
Cerebellar ataxia
Gait Ataxia
Ataxic Gait
Presentation (obstetrics)
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Peripheral neuropathy often occurs in cryoglobulinemia but the pathogenesis of the peripheral nerve involvement is not completely understood, so that the relation between the reported endoneural changes and neuropathy is not clear. In this study we compared the sural nerve biopsies of 6 cryoglobulinemic patients with or without signs of peripheral neuropathy and all affected by the essential mixed type II form (ECII) and, moreover, of 8 age-matched controls. We found that in all the patients with neuropathy, axonopathy occurred and it was invariably associated with endoneural vessel damage. Moreover, the fiber losses were patchily distributed within the nerve fascicles. On the contrary both nerve fibers and vessels were normal in the patients without clinical and neurophysiological evidence of neuropathy and in controls. Our results support the hypothesis that the endoneural damage observed during ECII is not simply coincidental, but is relevant in the pathogenesis of cryoglobulinemic neuropathy. They also favor the assumption that ischemic damage of the nerve fibers occurs during ECII.
Sural nerve
Pathogenesis
Entrapment Neuropathy
Nerve fiber
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We describe a patient with cerebellar ataxia of degenerative nature who was administered high-dose piracetam in a single-blind trial. Piracetam was demonstrated to be highly effective on tandem gait and gait ataxia in daily doses of 60 g. We suggest piracetam has a potential anti-ataxic effect in human cerebellar ataxia when used in considerably higher doses than those indicated for other purposes.
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Cerebellar ataxia
Gait Ataxia
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Friedreich's ataxia is a rare degenerative neuromuscular disorder, caused by a homozygous GAA triplet repeat expansion in the frataxin (FXN) gene, with a broad clinical phenotype characterized by progressive gait and limb ataxia, dysarthria, and loss of lower limb reflexes; cardiac involvement is represented by hypertrophic cardiomyopathy, ventricular arrhythmias, and sudden cardiac deaths. Currently, no definite therapy is available, while many drugs are under investigation; for this reasons, we need markers of short- and long-term treatment efficacy acting on different tissue for trial evaluation. We describe the case of a 21-year-old patient affected by Friedreich's ataxia on wheel-chair, with initial cardiac involvement and electrocardiographic features characterized by thiamine treatment-related negative T wave and QTc variations. We discuss plausible physiopathology and potential ECG role implications as an intermediate marker of treatment response in future clinical trials considering patients affected by Friedreich's ataxia.
Frataxin
Gait Ataxia
Dysarthria
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Cerebellar ataxia may arise as a consequence of autoimmune damage of the cerebellum. Adult patients with autoimmunity against the cerebellum often have an underlying neoplasm (paraneoplastic cerebellar degeneration). These patients commonly develop rapidly evolving severe ataxia and harbour serum and CSF onconeuronal antibodies (mainly anti-Hu, Yo, Ri, Tr). By contrast, antibodies to neuronal glutamic acid decarboxylase (GAD-Abs) have been reported in patients with a less severe form of non-paraneoplastic cerebellar ataxia.1 The finding of GAD-Abs in patients with paraneoplastic neurological symptoms associated with malignant tumours is very rare. Here we report a patient with thymic neuroendocrine carcinoma who developed progressive cerebellar ataxia with GAD-Abs.
A 55-year-old man came to our attention in May 2007 because of gait instability. He smoked 40 cigarettes a day. There was no family history of neurological or autoimmune disorders. In December 2006 he started noticing imbalance that slowly progressed over months and prompted him to use a cane to walk. On examination he had mild scanning dysarthria, horizontal gaze evoked nystagmus and mild limb dysmetria and dysdiadochokinesia. His gait was …
Dysmetria
Paraneoplastic cerebellar degeneration
Gait Ataxia
Cerebellar ataxia
Cerebellar Degeneration
Opsoclonus
Dysarthria
Ataxic Gait
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Friedreich's ataxia (FRDA) is the most frequent cause of recessive ataxias. Neurological examination shows oculo-motor ataxia, dysarthria, limbs ataxia, tendon areflexia, pyramidal signs and sensory deficits. Extra-neurological involvement consists in osteoarticular deformities, cardiomyopathy and diabetes mellitus. Neurological deficits and osteoarticular deformities both contribute to the gait disorder, which is the main disabling deficit. In 98% of the cases, a trinucleotide repeat is found in chromosome 9. Gene implicated in FRDA codes for a protein called frataxin. Experimental studies have revealed iron accumulation in mitochondria of neurons and cardiomyocytes, suggesting that frataxin plays a determinant role in intramitochondrial iron homeostasis. These discoveries are now considered as a clue for new strategies of treatment in this hereditary disease.
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Gait Ataxia
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Dysmetria
Gait Ataxia
Ataxic Gait
Cerebellar ataxia
Intention tremor
Neurological examination
Gait Disturbance
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Anti-glutamic acid decarboxylase (GAD) antibodies are described in stiff-person syndrome and also in other neurological syndromes, including cerebellar ataxia and epilepsy. This paper reports the case of a patient who had chronic focal epilepsy, upbeat nystagmus and cerebellar ataxia, associated with a polyautoimmune response including anti-GAD antibodies. Both gait and nystagmus improved markedly after immunosuppressive treatment with corticosteroids and azathioprine. After the introduction of benzodiazepines, previously refractory seizures were completely controlled. Anti-GAD antibodies should be actively sought out in pharmacoresistant epilepsy, particularly if other neurological abnormalities are present. Combined treatment with immunosuppressants and γhydroxybutyric acidergic agents may be highly effective.
Cerebellar ataxia
Stiff person syndrome
Gait Ataxia
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Cerebellar ataxia
Ataxic Gait
Gait Ataxia
Movement Disorders
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Abstract Background and purpose Neuronal autoantibodies can support the diagnosis of primary autoimmune cerebellar ataxia (PACA). Knowledge of PACA is still sparce. This article aims to highlight the relevance of anti‐neurochondrin antibodies and possible therapeutical consequences in people with PACA. Methods This is a case presentation and literature review of PACA associated with anti‐neurochondrin antibodies. Results A 33‐year‐old man noticed reduced control of the right leg in May 2020. During his first clinic appointment at our institution in September 2021, he complained about gait imbalance, fine motor disorders, tremor, intermittent diplopia and slurred speech. He presented a pancerebellar syndrome with stance, gait and limb ataxia, scanning speech and oculomotor dysfunction. Within 3 months the symptoms progressed. An initial cerebral magnetic resonance imaging, June 2020, was normal, but follow‐up imaging in October 2021 and July 2022 revealed marked cerebellar atrophy (29% volume loss). Cerebrospinal fluid analysis showed lymphocytic pleocytosis of 11 x 10 3 /L (normal range 0–4) and oligoclonal bands type II. Anti‐neurochondrin antibodies (immunoglobulin G) were detected in serum (1:10,000) and cerebrospinal fluid (1:320, by cell‐based indirect immunofluorescence assay and immunoblot, analysed by the EUROIMMUN laboratory). After ruling out alternative causes and neoplasia, diagnosis of PACA was given and immunotherapy (steroids and cyclophosphamide) was started in January 2022. In March 2022 a stabilization of disease was observed. Conclusion Cerebellar ataxia associated with anti‐neurochondrin antibodies has only been described in 19 cases; however, the number of unrecognized PACAs may be higher. As anti‐neurochondrin antibodies target an intracellular antigen and exhibit a mainly cytotoxic T‐cell‐mediated pathogenesis, important therapeutic implications may result. Because of the severe and rapid clinical progression, aggressive immunotherapy was warranted. This case highlights the need for rapid diagnosis and therapy in PACA, as stabilization and even improvement of symptoms are attainable.
Gait Ataxia
Cerebellar ataxia
Pleocytosis
Paraneoplastic cerebellar degeneration
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