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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 73 records · Page 4Linked to original sources
PubMed1998

Increased activation of frontal areas during arm movement in idiopathic torsion dystonia.

Most positron emission tomography (PET) studies of regional cerebral function in idiopathic torsion dystonia (ITD) have failed to show abnormalities, but there have been few studies of the changes in regional cerebral blood flow (rCBF) that occur during movement in dystonia. Using PET, we have studied six patients with familial generalized ITD both at rest and while moving a joystick with the right hand. The patterns of CBF change obtained were compared with those in six age-matched control subjects. In the dystonia group, free selection of movement was associated with relative increases in rCBF above that observed in control subjects in the left premotor area, the supplementary motor area (SMA), the anterior cingulate cortex, and the left dorsolateral prefrontal area. Subcortical increases were observed within the cerebellum and the putamen. There was a relative decrease in flow through the contralateral primary sensorimotor cortex. These findings contrast with those reported in patients with Parkinson's disease undertaking the same task in which the activity in the SMA and putamen was decreased. We suggest that arm dystonia in ITD is associated with overactivity of the premotor areas, including the SMA, and that this results from release of the thalamus from the normal inhibitory influence of the globus pallidus internal segment. Other abnormalities of basal ganglia control of brain stem centers may be involved in axial dystonia.

Adult↗
PubMed1998

Generalized chorea in two patients harboring the Friedreich's ataxia gene trinucleotide repeat expansion.

Recently, a trinucleotide repeat expansion in intron 1 of the frataxin gene on chromosome 9p13 has been identified as the genetic defect in Friedreich's ataxia (FA). We have identified two patients exhibiting generalized chorea in the absence of cerebellar signs who were homozygous for this intron 1 expansion. Chorea as a rare manifestation of FA has previously been controversial. This is the first report of chorea in patients confirmed to have the FA genetic abnormality and broadens further the clinical phenotype associated with the FA genotype.

Adolescent↗
PubMed1998

Young-onset Parkinson's disease revisited--clinical features, natural history, and mortality.

The authors report on clinical features and mortality rates in a group of 149 patients with apparent idiopathic parkinsonism starting before the age of 40 years. Ten had juvenile parkinsonism (JP; onset before age 21 years) and 139 had young-onset Parkinson's disease (YOPD; onset at age 21 to 40 years). Included were 60 patients originally reported 10 years ago. Fifty percent of the JP group had a positive family history of parkinsonism in a first-degree relative, and clinical presentation was heterogeneous. Mortality risk was threefold that of the normal population. In the YOPD group, the mortality risk was double that of the normal population. Poor initial response to L-dopa was a risk factor for early death. In two previously reported patients, the diagnosis had been changed to multiple system atrophy and Machado-Joseph disease. After a median disease duration of 18 years, cognitive impairment was found in only 19% of YOPD patients (13% of those younger than 60 years and 43% of those 60 years or older). Age was the most important factor for development of dementia, but female sex and positive family history of parkinsonism also had more modest predictive value. After a disease duration of 10 years or less, only 5% of patients were experiencing falls and 30% freezing, but all patients had developed L-dopa-related fluctuations and dyskinesias. The authors conclude that the mortality rate in parkinsonism starting before the age of 40 is increased in comparison to the normal population and is similar to the general Parkinson's disease population. Intellectual function and postural reflexes are usually well preserved for many years despite a long history of parkinsonism and the early and frequent occurrence of treatment complications, provided the patients remain biologically and chronologically young.

Adolescent↗
PubMed1998

Co-localization of P450 enzymes in the rat substantia nigra with tyrosine hydroxylase.

Susceptibility to develop Parkinson's disease has been linked to abnormalities of P450 enzyme function. Multiple P450 enzymes are expressed in brain but the relationship of these to Parkinson's disease is unknown. We have investigated the expression of P450 enzymes in the rat substantia nigra and their co-localization in tyrosine hydroxylase-positive neurons and astrocytes. Immunohistochemistry was performed using anti-peptide antisera against the following P450 enzymes: CYP1A1, CYP1A2, CYP2B1/2, CYP2C12, CYP2C13/2C6, CYP2D1, CYP2D4, CYP2E1, CYP3A1, CYP3A2 and NADPH-P450 oxidoreductase. Immunoreactivity in nigral cells was found only for CYP2E1 and CYP2C13/2C6. CYP2E1 immunoreactivity was localized to many midbrain nuclei including the substantia nigra pars compacta but not the substantia nigra pars reticulata while immunoreactivity to CYP2C13/2C6 was found in the substantia nigra pars compacta, substantia nigra pars reticulata and many other midbrain nuclei. Sections of rat midbrain double labelled for either CYP2E1 or CYP2C13/2C6 and tyrosine hydroxylase or glial fibrillary acidic protein were examined for co-localization by confocal laser scanning microscopy. CYP2E1 and CYP2C13/2C6 immunoreactivity was found in tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta but not in glial cells. CYP2C13/2C6, but not CYP2E1, was also found in non-glial, non-tyrosine hydroxylase-expressing cells in the substantia nigra pars reticulata. Isoniazid induction increased CYP2E1 fluorescence signal intensity from nigral dopaminergic neurons. At least two P450 enzymes are found in nigral dopamine containing cells and one, namely CYP2E1, is selectively localized to this cell population. CYP2E1 is a potent generator of free radicals which may contribute to nigral pathology in Parkinson's disease. The expression of CYP2E1 in dopaminergic neurons in substantia nigra raises the possibility of a causal association with Parkinson's disease.

Animals↗
PubMed1998

Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24.

Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently identified partial epilepsy in which two different mutations have been described in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4). An additional seven families are presented in which ADNFLE is unlinked to the CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no evidence of defective CHRNA4. One of the families showed evidence of linkage to 15q24, close to the CHRNA3/CHRNA5/CHRNB4 cluster (maximum LOD score of 3.01 with D15S152). Recombination between ADNFLE and CHRNA4, linkage to 15q24 in one family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and the two known CHRNA4 mutations are responsible for only a minority of ADNFLE. Although the ADNFLE phenotype is clinically homogeneous, there appear to be a variety of molecular defects responsible for this disorder, which will provide a challenge to the understanding of the basic mechanism of epileptogenesis.

Chromosome Mapping↗
PubMed1998

A study of medial pallidotomy for Parkinson's disease: clinical outcome, MRI location and complications.

We have studied the effects of unilateral ventral medial pallidotomy in 26 patients with medically intractable Parkinson's disease with marked drug-induced dyskinesias. Preoperatively, all patients were assessed during one 5-day admission according to the Core Assessment Programme for Intracerebral Transplantation (CAPIT) protocol, including rating in the 'practically defined off' and 'best on' states before and during a single-dose levodopa challenge. Motor performance was assessed with subset categories of the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a standard dyskinesia rating scale. Pallidotomy was performed under stereotaxic CT guidance with intra-operative extracellular microelectrode recording made from the basal ganglia. All patients were re-assessed 3 months postoperatively and a subgroup (n = 9) have so far also been re-assessed after 1 year. Pre- and postoperative performance scores were compared in order to determine which categories of performance improved postoperatively. Significance was accepted at P < 0.005 in order to take into account the multiple number of comparisons performed. Patient medication was compared pre- and postoperatively and the morbidity associated with surgery was also recorded. The most significant improvement postoperatively was the diminution of 'on' dyskinesias contralaterally (67%, P = 0.0001); however, ipsilateral (45%, P = 0.0006) and axial (50%, P = 0.0008) dyskinesias also improved. Contralateral to pallidotomy, the median 'off' motor UPDRS score improved by 27% (P = 0.001) and a significant improvement was also observed in contralateral rigidity by 25% (P = 0.001). There were trends towards improvement in contralateral tremor (33%, P = 0.016) and bradykinesia (24%, P = 0.013) scores. Ipsilateral rigidity improved by 22% (P = 0.005), but other ipsilateral motor scores did not alter significantly. The 'off' gait/postural instability score and 'off' walking time showed marginally significant improvements by 7% (P = 0.007) and 29% (P = 0.014), respectively. On medication, no significant postoperative improvements in parkinsonism were detected. Anti-parkinsonian medication increased by 11% postoperatively. In the subgroup who were available for assessment 1 year postoperatively, responses were generally maintained. Two (7.7%) of the 26 patients had fatal complications (one cerebral haemorrhage and one haemorrhagic infarct) directly related to surgery. Among the remaining 24 patients, four (15.4% of the total 26) had major complications (two persisting and two transient). Ten patients (38.5%) had minor complications. The majority of the complications (major and minor) occurred in the earlier operated patients and the complication rate subsequently declined with increasing operative experience. The remaining 10 patients (38.5%) had no significant side-effects. One of these 10 patients died from an incidental malignant glioma 6 months postoperatively. These findings confirm that levodopa-induced dyskinesias are dramatically reduced following ventral medial pallidotomy and constitute the principal indication for pallidotomy. Improvements in underlying parkinsonism were of smaller magnitude. Pallidotomy may also offer some patients an opportunity to increase antiparkinsonian medication. Patient selection for medial pallidotomy should, therefore, be based largely on anticipated improvements in levodopa-induced dyskinesias, but this must be balanced against the associated morbidity and mortality.

Aged↗
PubMed1998

The natural history of tardive dystonia. A long-term follow-up study of 107 cases.

The clinical picture, risk factors and natural history of tardive dystonia resulting from dopamine-receptor antagonist (DRA) treatment in 107 patients (57 male and 50 female), seen between 1972 and 1995, are described. The mean age at onset (+/- SD) was 38.3 +/- 13.7 years (range 13-68 years), and the age at last follow-up was 46.3 +/- 15.7 years (range 15-80 years). These patients had received DRAs for schizophrenia (39%), for other psychiatric conditions (51.5%) and for non-psychiatric disorders (9.5%). All classes of neuroleptics used were implicated in producing tardive dystonia, which was found to develop at any time, ranging from 4 days to 23 years after their introduction (median 5, mean 6.2 +/- 5.1 years); there was no 'safe' period. Men were significantly younger than women at onset of dystonia, which developed after shorter exposure in men. At onset, the dystonia was focal in 83% of cases, but progressed over months or years and remained focal in only 17% at the time of maximum severity. The craniocervical region was involved in 87% of cases, and was the most commonly affected site both at onset and at maximum severity. There was a correlation between the site and age of onset; the site of onset ascended from the lower limbs to the face as the mean age of onset increased. Overall, the phenomenology of tardive dystonia was indistinguishable from that of primary (idiopathic) dystonia, although retrocollis and anterocollis, as well as torticollis to the right, were significantly more common in tardive dystonia. It is a very persistent disorder; only 14% of our patients had a remission over a mean follow-up period of 8.5 years. Remission occurred after a mean of 5.2 years from onset (range 1-12 years) and 2.6 years after discontinuation of neuroleptics (range 1 month to 9 years). Discontinuation of neuroleptics increased the chances of remission fourfold. Patients with < or = 10 years on neuroleptics had a five times greater chance of remission than those with > 10 years exposure, suggesting that the pathogenetic changes in tardive dystonia may become irreversible after long-term use of these drugs. None of the numerous treatments tried in these patients, including clozapine and botulinum toxin injections, seemed to relate to overall outcome, but there was a significant negative association between the occurrence of remission and the use of benzodiazepines. Although there were hints of a possible genetic predisposition, the question as to whether patients with tardive dystonia have an underlying vulnerability remains unanswered.

Adolescent↗
PubMed1998

The role of DYT1 in primary torsion dystonia in Europe.

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. DYT1 on chromosome 9q34 was the first PTD gene to be mapped. A 3-bp (GAG) deletion in this gene was reported to account for almost all early limb-onset generalized PTD. No relationship has been found with DYT1 in patients with prominent craniocervical involvement. To elucidate the DYT1-associated phenotype, we analysed the DYT1 mutation in 150 PTD patients, either sporadic or index cases from small PTD families. Twenty-two patients were positive for the GAG deletion in the DYT1 gene. Fifteen of them presented with the typical DYT1 phenotype (early, limb-onset generalized dystonia without spread to craniocervical muscles), four had limb-onset dystonia with spread to craniocervical muscles, two patients had arm-onset segmental dystonia and one had focal right-arm dystonia. One-hundred and twenty-eight patients were negative for the DYT1 mutation. Forty-six of them had segmental dystonia and 59 had focal dystonia. The other 23 patients presented with generalized dystonia, either with craniocervical involvement (13 patients) or without spread to the craniocervical region (typical DYT1 phenotype-10 patients). These data confirm the importance of the GAG deletion in European cases of PTD, and indicate phenotypic and genotypic heterogeneity.

Adolescent↗
PubMed1998

Status dystonicus: the syndrome and its management.

Patients with dystonic syndromes sometimes develop increasingly frequent and relentless episodes of devastating generalized dystonia which we call status dystonicus. Twelve cases of status dystonicus, of various underlying aetiologies, are presented. Possible precipitating factors were identified in only five cases: intercurrent infection (one); discontinuation of lithium (one) and tetrabenazine (one); and the introduction of clonazepam (two). Nine patients required mechanical ventilation and three others were sedated with intravenous chlormethiazole. Drug therapy used included benzhexol, tetrabenazine, pimozide, baclofen, chlorpromazine, haloperidol, carbamazepine and acetozolamide. Two patients underwent thalamotomies, one of whom improved. Two patients died, five returned to their pre-status dystonicus condition, two eventually made a full recovery and three were worse. Patients with status dystonicus should be managed on an intensive care unit as they may develop bulbar and respiratory complications which may require ventilation. Metabolic problems encountered can include rhabdomyolysis with acute renal failure. Drug therapy with benzhexol, tetrabenazine and pimozide or haloperidol may be beneficial in some cases.

Adolescent↗
PubMed1998

Influence of vision on upper limb reaching movements in patients with cerebellar ataxia.

The effects of vision on spatial and temporal characteristics of free unrestrained reaching movements of the arm were examined in 17 patients with ataxic syndromes due to degenerative disease of the cerebellum and its connections. Subjects were required to reach out and touch a visually presented target either in the dark or with the target and their finger visible. Overall, patients had prolonged reaction times and their movements were performed slower than normal. The spatial paths described by their fingertips were more circuitous, being of greater length than normal, a characteristic that was uninfluenced by visual conditions. Ataxic movements were less accurate than normal in two ways. First, there was greater spatial variability between repeat paths to the same target. The increased variability was present very early in the movement trajectory and at that stage was not influenced by visual feedback. Secondly, there were large constant errors at the end of movement, but only when moving in darkness. Patients with Friedreich's ataxia as well as those with intrinsic cerebellar degeneration showed the above abnormalities, although there were some quantitative differences between the two groups. We suggest these spatial errors arise because the cerebellum contributes either directly or indirectly to preparatory motor processes which, based on limb proprioceptive and retinal information, compute the pattern of muscle activity required to launch the limb accurately towards a target. Patients were largely successful at using visual guidance to make midflight adjustments to their movements in order to improve accuracy. This manifested as a reduction in spatial variability between repeat paths as the target was approached and a reduction in constant error. However, the visual correction mechanism did not appear normal. Under visual guidance, the end-phase of movement was often prolonged and characterized by excessive deviations or direction changes in the path. These deviations may be the expression of a visual guidance system producing corrections which themselves contain error requiring further correction. Thus, this process may be abnormal for the same reason that the initial pattern of muscle activity is misjudged.

Adult↗
PubMed1998

Training improves the speed of aimed movements in Parkinson's disease.

In this study, the extent to which bradykinesia in patients with idiopathic Parkinson's disease can be influenced by practice and by specific training strategies was investigated. Fifteen patients with Parkinson's disease tested after withdrawal of anti-Parkinson medication, and 15 matched control subjects, practised a ballistic aiming task. Performance was tested before, during and after training and again 1 h later. The Parkinson's disease patients and control subjects were randomly assigned to one of two training schedules, practising with or without rhythmic auditory cues. At baseline, the Parkinson's disease patients showed longer movement times, with a marked decrease in maximum acceleration and deceleration in the initial open-loop phase compared with those of the control subjects. With training, they were able to make significant improvement in the speed of aimed movements, particularly in the early movement phase, without any deterioration in accuracy. These effects transferred to an untrained limb and were at least partially maintained after a 1-h delay. While patients remained impaired relative to control subjects at all phases of training and follow-up, the patients' performance at the end of training did not differ significantly from the control subjects' baseline function. Contrary to expectation, rhythmic auditory cues did not enhance improvement in the speed of aimed movements in either patients or control subjects. If anything, less improvement was shown in the cued groups, although there were suggestions that the aiming skill was retained better over the delay period. The results demonstrate preserved abilities to improve speed of single ballistic aiming movements in Parkinson's disease patients and the possibility of reducing bradykinesia by training.

Aged↗
PubMed1998

Abnormal motor unit synchronization of antagonist muscles underlies pathological co-contraction in upper limb dystonia.

The aim of this study was to examine the pathophysiological mechanisms underlying co-contraction in patients with dystonia (n = 6) and writer's cramp (n = 5). Multi-unit needle and surface EMGs were recorded from extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles during motor tasks that elicited dystonia or writer's cramp. The EMGs from ECR and FCR were recorded simultaneously and analysed using cross-correlation analysis. Similar recordings were obtained from healthy age- and sex-matched control subjects (n = 8). Despite co-contraction of the muscles, cross-correlograms from the healthy subjects did not reveal evidence of motor unit synchronization. Cross-correlograms from the dystonic subjects revealed a central peak with a median duration of 37 ms, indicating broad-peak motor unit synchronization. Cross-correlograms from patients with writer's cramp were either flat or modulated by a 11-12-Hz tremor. Frequency-domain analysis of ECR and FCR EMGs demonstrated significant coherence in the patients with dystonia and writer's cramp. These results indicate that co-contraction in dystonia is neurophysiologically distinct from voluntary co-contraction and is produced by abnormal synchronization of presynaptic inputs to antagonist motor neuron pools. ECR and FCR co-contraction in writer's cramp may be a compensatory process under voluntary control.

Adolescent↗
PubMed1998

Central motor conduction time in progressive multiple sclerosis. Correlations with MRI and disease activity.

The purpose of this study was to relate abnormalities of motor conduction time to the presence of spinal cord MRI lesions in progressive multiple sclerosis and to investigate the relationship between changes in motor conduction over time and clinical and MRI changes. Central motor conduction time (CMCT), serial MRI of the brain and spinal cord, and clinical evaluations were carried out in 20 patients with primary and secondary progressive multiple sclerosis. CMCT was carried out at the beginning and end of the study whilst the clinical and MRI examinations occurred at monthly intervals for 12 months. Median CMCT to abductor pollicis brevis was 14.8 ms (range 8.8-27.4 ms). The response latency to tibialis anterior correlated with disability measured on the Expanded Disability Status Scale. Latencies to upper limb muscles correlated with cervical MRI lesion load and the presence of atrophy of the cervical cord. Over the 12-month study period, 15 of 19 patients deteriorated clinically. However, an increase in motor response latencies occurred only in the four patients who had developed new cord lesions. The results suggest that prolonged CMCT is related to spinal cord lesion load and that, over time, changes in the CMCT occur only when spinal cord lesion load increases. Clinical change in progressive multiple sclerosis may therefore occur without either the development of new lesions on MRI scans or an increase in motor conduction time. This suggests that clinical deterioration in these patients may occur by a mechanism other than increasing demyelination. This may be progressive axonal degeneration.

Adult↗
PubMed1998

The pathophysiology of primary dystonia.

Co-contraction and overflow of EMG activity of inappropriate muscles are typical features of all dystonic movements whether voluntary or involuntary. Voluntary movements are slow and more variable than normal, and there is particular difficulty switching between component movements of a complex task. Reduced spinal cord and brainstem inhibition is common to many reflex studies (long-latency reflexes, cranial reflexes and reciprocal inhibition). These reflex abnormalities may contribute to the difficulties in voluntary movements but cannot be causal as they can occur outside the clinically involved territory. Clinical and neurophysiological studies have emphasized the possible role of sensory feedback in the generation of dystonic movements. Abnormalities of cortical and basal ganglia function have been described in functional imaging and neurophysiological studies of patients with dystonia and in animal models of primary dystonia. Studies of cortical function have shown reduced preparatory activity in the EEG before the onset of voluntary movements, whilst magnetic brain stimulation has revealed changes in motor cortical excitability. Functional imaging of the brain in primary dystonia has suggested reduced pallidal inhibition of the thalamus with consequent overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex during movements. These findings are supported by preliminary neuronal recordings from the globus pallidus and the thalamus at the time of stereotaxic surgery in patients with dystonia. All this evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata). This causes altered thalamic control of cortical motor planning and executive areas, and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.

Animals↗
PubMed1998

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD).

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha-synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha-synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.

Adult↗
PubMed1998

Exercise induced steroid dependent dystonia, ataxia, and alternating hemiplegia associated with epilepsy.

This paper describes a 20 year old woman with a new combination of neurological impairments in which the motor phenomena were responsive to corticosteroid treatment. She had lifelong moderate learning impairment. A variable ataxia with cerebellar characteristics was present from early life, with early severe exacerbation when seizures were uncontrolled. Atypical absence and simple and complex partial seizures were present from the first year of life and EEG abnormalities were maximal in the right parietal region, concordant with a mild non-specific abnormality of the white matter in the region of the trigone. Episodes of alternating hemiplegia occurred from 11 years, unassociated with seizures. Exercise induced dystonia occurred from the age of 5. After 10-20 minutes walking, her right foot would turn in and the right leg would stiffen, followed by the left and by falling and inability to get up for several minutes. Prednisolone improved her ataxia and was associated with cessation of both seizures and exercise induced dystonia. This adds a new syndrome to the corticosteroid responsive motor disorders associated with epilepsy.

Adolescent↗
PubMed1998

Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity.

OBJECTIVE: To investigate whether the stiff limb syndrome may be separated from the stiff man syndrome and progressive encephalomyelitis with rigidity on simple clinical grounds, and whether such a distinction has implications for aetiology, treatment, and prognosis. METHODS: Twenty three patients referred over a 10 year period with rigidity and spasms in association with continuous motor unit activity, but without evidence of neuromyotonia, extrapyramidal or pyramidal dysfunction or focal lesions of the spinal cord were reviewed. The patients were divided into those with an acute or subacute illness, leading to death within 1 year, and those with a chronic course. The latter were divided into those in whom rigidity and spasms dominated in the axial muscles, or in one or more distal limbs, at the time of their first assessment. RESULTS: This simple division identified three distinct groups of patients. (1) Progressive encephalomyelitis with rigidity: two patients had a rapidly progressive condition characterised by widespread rigidity which resulted in death within 6 and 16 weeks. One patient had negative anti-GAD and anti-neuronal antibodies, but had markedly abnormal CSF and widespread denervation. The principal pathological findings in this case were a subacute encephalomyelitis which primarily affected the grey matter. In the remaining patient anti-GAD antibodies were not tested, and postmortem was refused. (2) Stiff man syndrome: eight patients had rigidity and painful spasms of the lumbar paraspinal, abdominal, and occasionally proximal leg muscles associated with a lumbar hyperlordosis. There was no involvement of the upper limbs, distal lower limbs, sphincters or cranial nerves. Seven had anti-GAD antibodies and most had additional evidence of autoimmune disease. Neurophysiologically there was continuous motor unit activity with abnormal exteroceptive reflexes, but a normal interference pattern during spasms. The patients all responded to baclofen/diazepam and remained ambulant. (3) Stiff limb syndrome: thirteen patients had rigidity, painful spasm, and abnormal postures of the distal limb, ususphincter or brainstem involvement. Generalised myoclonic jerks were not a feature. Only two had truncal rigidity, and another two had anti-GAD antibodies. Most had no evidence of autoimmune disease. Neurophysiologically they had continuous motor unit activity in the affected limb, abnormal exteroceptive reflexes, and abnormally segmented EMG activity during spasms. The disease ran a protracted course, and most patients had only a partial response to baclofen or diazepam. About half became wheelchair bound. CONCLUSIONS: The stiff limb syndrome seems distinct from the stiff man syndrome or progressive encephalomyelitis with rigidity, and is an important cause of rigidity and spasm in the setting of continuous motor unit activity.

Adult↗