Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and pathological features, including electron microscopy of a sporadic case of neuroaxonal dystrophy with findings of both Hallervorden-Spatz syndrome (HS) and Seitelberger's disease (SD) are presented. The patient presented with a slowly progressive illness with seizures, extrapyramidal symptoms, cerebellar ataxia, dementia, spasticity, myoclonic movements and a severe demyelinating peripheral neuropathy with secondary muscular atrophy. Neuropathological examination disclosed cerebral and cerebellar atrophy and excessive pigmentation of the globus pallidus and substantia nigra. Spheroids were widely distributed within the central and peripheral nervous system. Numerous neurofibrillary tangles (NFTs) were found within the hippocampal cortex, neocortex and brain stem. Extensive granulovacuolar degeneration (GVD), Hirano bodies and Lewy bodies were also demonstrated. Severe loss of myelin from the peripheral nerves and muscular denervation were striking features. We wish to report this case which shares findings of both entities, HSS and SD.
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PMID:Adult onset Hallervorden-Spatz syndrome or Seitelberger's disease with late onset: variants of the same entity? A clinico-pathological study. 236 93

The arguments over the nomenclature of the syndrome are reviewed. Ethical considerations favour replacing the present eponyms with the title of panthothenate kinase-associated neurodegeneration (PKAN), now that more is known about the cause of the condition. The symptoms and signs of the syndrome are described, and these can present from infancy to adult life. Dystonia, involuntary movements and spasticity are prominent causes of disability. If the onset is delayed the presentation can be unusual. Tests that can help in diagnosis are reviewed, especially the "eye of the tiger" revealed by magnetic resonance imaging scanning. Death usually occurs about 10 years after the onset, but the course may be more prolonged. The findings on autopsy are also considered, with the typical findings of iron pigment deposits and axonal spheroids. Then the causes are discussed. Once the responsible gene PANK2 had been discovered on chromosome 20 it was found that this encoded for pantothenate kinase which is essential for the synthesis of coenzyme A from pantothenate; and this is integral to fatty acid synthesis and energy metabolism. Also this can lead to a concentration of cysteine in the basal ganglia, and then to an accumulation of iron in these areas. The cysteine-iron complex will result in tissue damage by promoting oxidative stress, as in some other neurodegenerative diseases. The syndrome of PKAN can therefore be identified as a disorder of pantothanate, vitamin B5, metabolism. Infantile neuroaxonal dystrophy is briefly described as there have been suggestions that it is a variety of PKAN, but the evidence is in favour of the two diseases being separate entities. There may as yet be no specific treatment for this syndrome, but much can be done to help these children. Drugs may be needed to control epilepsy, and when dystonia is severe it may be possible to alleviate this by medical or surgical means. Also there will be other problems needing expert management, such as the provision of alternative means of communication if dysarthria is marked. The hope for the future is that now the cause has been found it will be possible to use methods such as antioxidative therapy and gene induction procedures.
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PMID:Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz syndrome). 1237 76

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disorder characterized by infantile onset and rapid progression of psychomotor regression and hypotonia evolving into spasticity. The neuroradiologic hallmark of the disease is represented by cerebellar atrophy and signal hyperintensity in the cerebellar cortex on MR T2-weighted images. We report a 2-year-old boy with psychomotor regression and hypotonia carrying a homozygous 5' splice site mutation in PLA2G6 gene, whose brain MRI revealed cerebellar atrophy with normal cerebellar cortex signal intensity. The absence of the signal hyperintensity of the cerebellar cortex does not rule out the diagnosis of INAD.
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PMID:Cerebellar atrophy without cerebellar cortex hyperintensity in infantile neuroaxonal dystrophy (INAD) due to PLA2G6 mutation. 1725 19

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disorder characterized by infantile onset and rapid progression of psychomotor regression and hypotonia evolving into spasticity. The neuroradiologic hallmark of the disease is represented by progressive cerebellar atrophy. Prior to the discovery of mutations in the PLA2G6 gene in family with INAD, the clinical diagnosis of the disease had been confirmed by the presence of spheroid bodies (SB) in a peripheral nerve biopsy. Various studies have found that some patients with mutations lacked SB and some without mutations had SB, indicating incomplete detection using either pathologic or molecular methods (7). This, together with the observation that the spectrum of clinical features associated with mutations in PLA2G6 is broader than previously described, has increased the usefulness of Magnetic Resonance (MR) in INAD diagnosis, particularly in the frequent occurrence of atypical cases, especially in the early stages of the disease. We retrospectively reviewed the MR studies of eight patients in whom clinical and imaging onset met the typical criteria for INAD. Their clinical and MR imaging (MRI) onset and follow-up were evaluated together with the neuroradiological findings reported in the literature in order to identify MRI features useful in differentiating INAD from other diseases with similar clinical onset and to discuss which of them are the most important, thus suggesting INAD diagnosis. Our contribution included the use of Proton Spectroscopy ((1)H-MR), diffusion weighted MR imaging (DWI) and diffusion tensor imaging (DTI) in the follow-up of seven of the eight patients. The literature reviewed included attempts to correlate clinical and MR data with the genotype in the group of patients carrying PLA2G6 mutations. From the limited and inhomogeneous cohort of patients included in our study, a correlation between the MR features, phenotype and genotype was not exhaustive.
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PMID:MRI Findings in Patients with Clinical Onset Consistent with Infantile Neuroaxonal Dystrophy (INAD), Literature Review, Clinical and MRI Follow-up. 2405 9

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the phospholipase A2 group 6 (Pla2G6) gene. Affected individuals usually present between the ages of 6 months and 2 years with rapid cognitive and motor regression and axial hypotonia. Gait disturbance, limb spasticity, cerebellar signs, and optic atrophy are other common features associated with INAD. Although magnetic resonance imaging (MRI) can sometimes contribute towards the diagnosis, the confirmation of INAD is by Pla2G6 gene analysis. In this case report, we describe the first individual (female) with INAD due to a combination of uniparental heterodisomy and isodisomy; we discuss the possible underlying mechanism and highlight the importance of parental carrier testing in accurately predicting the recurrence risk in these families. We also confirm the recent report of hypertrophy of the clava (also known as the 'gracile tubercle') as a useful MRI sign in INAD.
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PMID:Infantile neuroaxonal dystrophy caused by uniparental disomy. 2462 89

Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder characterized by infantile onset and rapid progression of psychomotor regression and hypotonia evolving into spasticity and dementia. Although nystagmus is a well-established neurological sign in infantile neuroaxonal dystrophy, it is mainly described as pendular and noticed in later stages of the disease. We report a 13-month-old girl with infantile neuroaxonal dystrophy harboring a compound heterozygous mutation in the PLA2G6 gene with downbeat nystagmus as the only presenting symptom. Our case indicates that downbeat nystagmus can be a rare but very early onset sign of cerebellar involvement in infantile neuroaxonal dystrophy and can anticipate the appearance of psychomotor regression and neuroradiological abnormalities.
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PMID:Downbeat nystagmus as the presenting symptom of infantile neuroaxonal dystrophy: a case report. 2480 Sep 72

Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder characterized by infantile onset of rapid motor and cognitive regression and hypotonia evolving into spasticity. Recessively inherited mutations of the PLA2G6 gene are causative of infantile neuroaxonal dystrophy and other PLA2G6-associated neurodegeneration, which includes conditions known as atypical neuroaxonal dystrophy, Karak syndrome and early-onset dystonia-parkinsonism with cognitive impairment. Phenotypic spectrum continues to evolve and genotype-phenotype correlations are currently limited. Due to the overlapping phenotypes and heterogeneity of clinical findings characterization of the syndrome is not always achievable. We reviewed the most recent clinical and neuroradiological information in the way to make easier differential diagnosis with other degenerative disorders in the paediatric age. Recognizing subtle signs and symptoms is a fascinating challenge to drive towards better diagnostic and genetic investigations.
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PMID:Infantile neuroaxonal dystrophy and PLA2G6-associated neurodegeneration: An update for the diagnosis. 2788 48

Infantile neuroaxonal dystrophy 1 (INAD) (OMIM #256600) is a rare infantile onset neurodegenerative disease characterised by neuroregression and hypotonia, evolving into generalized spasticity, blindness and dementia. We report our diagnostic approach of a pair of siblings with psychomotor regression, hypotonia, optic atrophy and auditory neuropathy. The brain magnetic resonance imaging (MRI) showed progressive cerebellar atrophy. Genetic testing of the PLA2G6 confirmed presence of compound heterozygous novel mutations. As the variant c. 196C>T (p.Gln66X) was a truncating variant, it was considered as pathogenic while the variant c. 2249G>A (p. Cys750Tyr) was considered as "likely pathogenic" by bioinformatics analyses. Our patient expands the clinical phenotype of INAD as it described the first South-East Asian patient with INAD-associated auditory neuropathy. Our report highlights the importance of increased awareness of this condition amongst clinicians, the use of deep phenotyping using neuroimaging and the clinical utility of gene sequencing test in the delineation of syndromes associated with infantile neurodegenerative disease.
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PMID:Infantile neuroaxonal dystrophy in a pair of Malaysian siblings with progressive cerebellar atrophy: Description of an expanded phenotype with novel PLA2G6 variants. 3149 91