Ataxia cerebellar

Leigh s syndrome (subacute necrotizing encephalomyelopathy) is characterized by a variable combination of clinical abnormalities including cerebellar ataxia, developmental delay, mental regression, deafness, optic atrophy, hypotonia, and... 

Myoclonic epilepsy with ragged-red fibers (MERPF) is a rare syndrome which shows clear maternal inheritance and a variable clinical pattern including progressive myoclonus, cerebellar ataxia, dementia, and muscle weakness. It is associated with an A-to-G transition at position 8344 of the tRNA Lys gene in the mtDNA. The mutation is heteroplasmic and produces similar multicomplex deficiencies as are seen in KSS. 

Boor JW, Hurtig HI Persistent cerebellar ataxia after exposure to toluene. Ann Neurol 2 440 42, 1977... 

In patients with ataxia-telangiectasia, an autosomal recessive disease in humans resulting in the development of cerebellar ataxia and lymphoreticular neoplasms, there appears to exist an increased sensitivity to damage by x-ray. Patients with Fanconi s anemia, an autosomal recessive anemia characterized also by an increased frequency of cancer and by chromosomal instability, probably have defective repair of cross-linking damage. 

Diagnosis of a urea cycle defect in the older child can be elusive. Patients may present with psychomotor retardation, growth failure, vomiting, behavioral abnormalities, perceptual difficulties, recurrent cerebellar ataxia and headache. It is therefore essential to monitor the blood ammonia in any patient with unexplained neurological symptoms, but hyperammonemia is inconstant with partial enzymatic defects. Measurement of blood amino acids and urinary orotic acid is indicated. 

Patients with sialidosis show a striking syndrome characterized by action myoclonus, cerebellar ataxia and a macular cherry red spot similar to that in Tay-Sachs disease but with preserved intellect. 

Durr, A., Smadja, D., Cancel, G. et al Autosomal dominant cerebellar ataxia type I in Martinique (French West Indies). Clinical and neuropathological analysis of 53 patients from three unrelated SCA2 families. Brain 118 1573-1581,1995. 

Zhuchenko, O., Bailey, J., Bonnen, R et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alA-voltage-dependent calcium channel. Nat Genet. 15 62-69,1997. 

Boder E, Sedgwick RP (1958) Ataxia-telangiectasia a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics 21(4) 526-554 Brown EJ, Baltimore D (2003) Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17(5) 615-628... 

The toxicities of 5-fluorouracil vary with the schedule and mode of administration. Nausea is usually mild if it occurs at all. Myelosuppression is most severe after intravenous bolus administration, with leukopenia and thrombocytopenia appearing 7 to 14 days after an injection. Daily injection or continuous infusion is most likely to produce oral mucositis, pharyngitis, diarrhea, and alopecia. Skin rashes and nail discoloration have been reported, as have photosensitivity and increased skin pigmentation on sun exposure. Neurological toxicity is manifested as acute cerebellar ataxia that may occur within a few days of beginning treatment. 

Cytarabine Inhibits DNA chain elongation, DNA synthesis and repair inhibits ribonucleotide reductase with reduced formation of dNTPs incorporation of cytarabine triphosphate into DNA AML, ALL, CML in blast crisis Nausea and vomiting, myelosuppression with neutropenia and thrombocytopenia, cerebellar ataxia... 

Central and/or peripheral nervous system involvement is one of the most frequent features, often resulting in the neonatal period in drowsiness, poor sucking, severe hypotonia, abnormal movements, seizures, respiratory distress, and fatal keto-acidotic coma with lactic acidosis [3]. To these severe conditions echo late-onset diseases now frequently attributed to or associated with mitochondrial OXPHOS defects, such as Alzheimer s or Parkinsons disease [10]. Major neurological symptoms, in variable combinations, involve trunk hypotonia, cranial nerve and brainstem involvement (with abnormal eye movements, ophthalmoplegia, recurrent apneas), cerebellar ataxia, myoclonia, seizures, pyramidal syndrome, peripheral neuropathy, poliodystrophy, and leukodystrophy infections [27,28]. A diffuse impairment of the cerebral white matter (leukodystrophy) mostly results in motor disturbance with mental retardation and low incidence of seizures. 

Kearns-Sayre syndrome [17] A multisystem disorder characterized by the invariant triad onset before age 20 years, PEO, pigmentary retinal degeneration plus at least one of the following complete heart block, cerebrospinal fluid protein above 100 mg/dl, cerebellar ataxia. Large-scale heteroplasmic mitochondrial DNA deletions are frequently detected in skeletal muscle (rarely in other tissues). 

Ramaekers VT, Hausler M, Opladen T, Heimann G, Blau N (2002) Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydro-folate in cerebrospinal fluid a novel neurometabolic condition responding to folinic acid substitution. Neuropediatrics 33 301-308... 

Artuch R., Brea-Calvo G., Briones P., Aracil A., Galvan M., Espinos C., Corral J., Volpini V., Ribes A., Andreu A. L., Palau F., Sanchez-Alcazar J. A., Navas P., and Pineda M. (2006). Cerebellar ataxia with coenzyme Qio deficiency diagnosis and follow-up after coenzyme Qio supplementation. J. Neurol. Sci. 246 153-158. 

Table 1. CACNA1A (Ca 2.1, a 1A) Functional results for mutations associated with FHM = familial hemiplegic migraine, EA2 = episodic ataxia type 2, SCA6 = spinocerebellar ataxia type 6, PCA = progressive cerebellar ataxia (although addition mutations have been associated with these disorders, only those with reported functional data are listed)...

Ishikawa K, Tanaka H, Saito M, Ohkoshi N, Fujita T, Yoshizawa K, Ikeuchi T, Watanabe M, Hayashi A, Takiyama Y, Nishizawa M, Nakano I, Matsubayashi K, Miwa M, Shoji S, Kanazawa I, Tsuji S, Mizusawa H (1997) Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19pl3.1-pl3.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19pl 3.1. Am J Hum Genet 61 336-346. 

Cytarabine 100 mg/m2/d for 5-10 days, either by continuous IV infusion or SC every 8 hours. Nausea and vomiting, bone marrow depression, stomatitis, and cerebellar ataxia... 

It is well established that mitochondrial function defects are not severe until the proportion of mutant mtDNA reaches a high level, which forms the basis of the concept of the threshold effect. In skeletal muscle, the level of the A3243G mutation is related to the severity of strokelike episodes, epilepsy, and dementia in patients with MELAS syndrome (C6, H14, PI). Similarly, the level of the A8344G mutation is correlated with the degree of cerebellar ataxia and myoclonus in patients with MERRF syndrome (C6). Thus, molecular genetic analysis of mtDNA mutations in muscle biopsies usually provides more definitive diagnosis of... 

B5. Baron, D. N., Dent, C. E., Harris, H., Hart, E. W., and Jepson, J. B., Hereditary pellagra-like skin rash with temporary cerebellar ataxia, constant renal aminoaciduria, and other bizarre biochemical features. Lancet ii, 421-428 (1956). 

Burk K, Bosch S, Muller CA, Melms A, Ziihlke C, Stern M, et al. Sporadic cerebellar ataxia associated with gluten sensitivity. Brain 2001 124 1013-1019. 

Sillevis Smitt P, Kinoshita A, De Leeuw B, Moll W, Coesmans M, Jaarsma D, et al. Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor. N Engl J Med 2000 342(1) 21 27. 

Irreversible neurotoxicity can occur at relatively low serum doses. Lang and Davis (2002) described the case of a 44 year old man who presented with a two-month history of dysarthria, ataxia and leg weakness whilst on maintenance lithium for bipolar disorder. He had significant cerebellar and pyramidal dysfunction. His serum lithium was 1.5 mmol/L, a moderate elevation for this patient. His recovery was only partial, leaving him mainly with cerebellar ataxia. The authors warned about the insidious onset of persistent neurotoxicity during routine treatment. 

Myoclonus due to maprotiline has been reported (13). Further neuromuscular symptoms that have been reported with maprotiline include cerebellar ataxia in a 54-year-old man with a history of unipolar depression and chronic alcohol abuse who was taking maprotiline 200 mg/day (14). The question of whether his history of alcohol abuse contributed by sensitizing his cerebellum to maprotiline-induced ataxia was unresolved. 

A 30-year-old man with bipolar affective disorder was given intravenous sodium valproate 20 mg/kg/day without any major problem. Later, he was given oral haloperidol 10 mg bd for persistent aggressive behavior and manic symptoms. The next day he developed a sense of imbalance and started swaying. He was drowsy and had cerebellar ataxia. Haloperidol was withdrawn and within 1 day his ataxia had disappeared completely in spite of continuing valproate. 

Ranjan S, Jagadheesan K, Nizamie SH. Cerebellar ataxia with intravenous valproate and haloperidol. Aust NZ J Psychiatry 2002 36(2) 268. 

These advantages are important in treating particular groups of patients, including patients with brain injury, elderly people, forensic populations, and the medically ill (11,12). On the other hand, over 50% of patients with cerebellar ataxia reported significant adverse effects, as described above (SEDA-21, 39). 

In both groups of patients, the only source of vitamin E for peripheral tissues will be recently ingested vitamin E in chylomicrons. They develop cerebellar ataxia, axonal degeneration of sensory neurons, skeletal myopatby, and pigmented retinopatby similar to those seen in experimental animals. 

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