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

Electrical stimulation of the spinal cord can be used for treatment of intractable pain and spasticity. Based on our experimental findings cervical spinal cord stimulation (cSCS) was performed on eight patients with severe brain dysfunction due to traffic accidents, pronounced vasospasm caused by subarachnoid hemorrhage or surgery of huge cerebral tumors (chordoma). After a 1 to 2 month period of stimulation, two patients became conscious and began to speak. It remains unclear whether cSCS induced the restoration of consciousness and improved neurological deficits. Although the successful results might be due to chance, cSCS might have stimulated brain function. This preliminary report shows such excellent results that further studies are warranted.
 ...
PMID:Beneficial effects of cervical spinal cord stimulation (cSCS) on patients with impaired consciousness: a preliminary report. 247 57

A family is described with familial myoclonic epilepsy associated with mitochondrial myopathy. The disorder follows a maternal inheritance pattern consistent with a mitochondrial DNA (mtDNA) mutation. The large kindred permitted exclusion of autosomal dominant, recessive, and X-linked patterns of transmission. Several characteristics of the inheritance and variability of expression within the pedigree are consistent with recently acquired knowledge about the genetics of human mtDNA. The clinical spectrum of disease is compatible with a proportionality model of mutant and wild-type mtDNAs. Muscle biopsies of affected patients showed an increased number of abnormal muscle mitochondria. Serum levels of pyruvate or pyruvate and lactate were elevated. The most severely affected patient had constant myoclonic jerking, dementia, ataxia, spasticity, hearing loss, and hypoventilation. Cerebral dysfunction in patients with mild involvement was marked by prominent photic driving seen on electroencephalograms and high-amplitude visual and somatosensory evoked responses but no myoclonus, ataxia, or dementia. The individual clinical features of the disease worsen over time for all patients; however, mildly affected patients have not become moderately affected and moderately affected patients have not become severely affected.
 ...
PMID:Maternally inherited mitochondrial myopathy and myoclonic epilepsy. 392 81

A 29-year-old man developed vertigo, diplopia, confusion and spasticity. Brain biopsy revealed multifocal microinfarcts. Bilateral hearing loss and retinal microangiopathy were also noted. Deficits were stable years after onset. Repeated neuropsychological testing was suggestive of diffuse cerebral dysfunction, with likely prominent involvement of reciprocal diencephalic-cortical projections.
 ...
PMID:Susac's syndrome: neuropsychological characteristics in a young man. 871 93

Neurophysiologic abnormalities are frequently seen in organic acidemias, but knowledge of the specific changes in the different types of organic acidemias is lacking. We studied electroencephalogram (EEG), visual evoked potential (VEP) and brain-stem auditory evoked response (BAER) in seven children with glutaric aciduria type I (GA1) to assess the neurophysiologic features in this rare inborn error of metabolism. Age at the time of the diagnosis ranged between 3 months and 36 months. Age at the time of neurophysiologic evaluation ranged between 11 months and 36 months. At the time of neurophysiologic evaluation, severe global developmental delay was seen in four patients, dystonia in four patients, motor delay in two patients, and axial hypotonia in two patients; macrocephaly, spasticity, moderate mental retardation and borderline intelligence were each seen in one patient. One patient had autistic features characterized by lack of language and social skills, poor eye contact and stereotypical behavior. Three of seven patients showed abnormal EEG findings. Two patients showed asymmetry with intermittent occipital delta slowing in one hemisphere. This finding probably indicates underlying cerebral dysfunction, and is not a specific feature. However, it suggests that these patients may develop abnormal EEG features during the course of the disease, and thus a baseline EEG may be useful for comparison over time. One patient showed high amplitude bursts of beta in the occipital regions with left predominance while on clonazepam and baclofen. We believe this finding was due to medication effect, and that what we observed was an exaggarated response to benzodiazepine. The clinical significance of this finding is unclear. VEP and BAER were available in four patients, and we found abnormalities in three of them. Neurophysiologic evaluation may be helpful in patients with GA1 as in other types of organic acidemias to help detect subtle changes that are not reflected by neurological examination or neuroimaging studies, and it may guide future treatment plans. Detailed neurophysiologic analysis in a large series of GA1 may yield further information regarding the extent of cerebral dysfunction.
 ...
PMID:Neurophysiologic features in glutaric aciduria type I. 1605 56

Motor disturbances are very common in paediatric neurology. Often families can be reassured that these are just variants of normal development. However, abnormal movements can also be the hallmark of severe brain dysfunction of different and complex origins. This review concentrates on motor disturbances as frequent and important symptoms of inborn errors of metabolism. A structured diagnostic approach is developed taking into account age-dependent physiological developments and pathophysiological responses of gross and fine motor functions. A series of investigations are presented with the primary aim of early diagnosis of treatable conditions. The correct recognition and differentiation of movement disorders (ataxia, rigid akinetic syndrome (Fparkinsonism_), dystonia, athetosis, tremor,and others), spasticity, and neuromuscular disorders, requires profound neurological expertise. A high level of suspicion and close interaction between paediatric neurologists and specialists in inborn errors of metabolism are indispensable to effectively and timely identify patients in whom motor disturbances are the presenting and/or main symptom of an inborn error.
 ...
PMID:Inborn errors of metabolism and motor disturbances in children. 1973 Oct 74

Complete arginase I deficiency is the least severe urea cycle disorder, characterized by hyperargininemia and infrequent episodes of hyperammonemia. Patients suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation and seizures, and is associated with intellectual disability. In mice, onset is heralded by weight loss beginning around day 15; gait instability follows progressing to inability to stand and development of tail tremor with seizure-like activity and death. Here we report that hyperargininemic mice treated neonatally with an adeno-associated virus (AAV)-expressing arginase and followed long-term lack any presentation consistent with brain dysfunction. Behavioral and histopathological evaluation demonstrated that treated mice are indistinguishable from littermates, and that putative compounds associated with neurotoxicity are diminished. In addition, treatment results in near complete resolution of metabolic abnormalities early in life; however, there is the development of some derangement later with decline in transgene expression. Ammonium challenging revealed that treated mice are affected by exogenous loading much greater than littermates. These results demonstrate that AAV-based therapy for hyperargininemia is effective and prevents development of neurological abnormalities and cognitive dysfunction in a mouse model of hyperargininemia; however, nitrogen challenging reveals that these mice remain impaired in the handling of waste nitrogen.
...
PMID:AAV-based gene therapy prevents neuropathology and results in normal cognitive development in the hyperargininemic mouse. 2338 1

Motor control and body representations in the central nervous system are built, i.e., patterned, during development by sensorimotor experience and somatosensory feedback/reafference. Yet, early emergence of locomotor disorders remains a matter of debate, especially in the absence of brain damage. For instance, children with developmental coordination disorders (DCD) display deficits in planning, executing and controlling movements, concomitant with deficits in executive functions. Thus, are early sensorimotor atypicalities at the origin of long-lasting abnormal development of brain anatomy and functions? We hypothesize that degraded locomotor outcomes in adulthood originate as a consequence of early atypical sensorimotor experiences that induce developmental disorganization of sensorimotor circuitry. We showed recently that postnatal sensorimotor restriction (SMR), through hind limb immobilization from birth to one month, led to enduring digitigrade locomotion with ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and clear signs of spinal hyperreflexia in adult rats, suggestive of spasticity; each individual disorder likely interplaying in self-perpetuating cycles. In the present study, we investigated the impact of postnatal SMR on the anatomical and functional organization of hind limb representations in the sensorimotor cortex and processes representative of maladaptive neuroplasticity. We found that 28 days of daily SMR degraded the topographical organization of somatosensory hind limb maps, reduced both somatosensory and motor map areas devoted to the hind limb representation and altered neuronal response properties in the sensorimotor cortex several weeks after the cessation of SMR. We found no neuroanatomical histopathology in hind limb sensorimotor cortex, yet increased glutamatergic neurotransmission that matched clear signs of spasticity and hyperexcitability in the adult lumbar spinal network. Thus, even in the absence of a brain insult, movement disorders and brain dysfunction can emerge as a consequence of reduced and atypical patterns of motor outputs and somatosensory feedback that induce maladaptive neuroplasticity. Our results may contribute to understanding the inception and mechanisms underlying neurodevelopmental disorders, such as DCD.
 ...
PMID:Early movement restriction leads to maladaptive plasticity in the sensorimotor cortex and to movement disorders. 3039 22