Two cases of unexpected long-term improvement of Parkinson's disease after subthalamic nucleus deep brain stimulation removal.

Two patients with Parkinson's disease (PD) treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS) for 3-4 years are reported, who demonstrated a persistent improvement following removal of STN-DBS for late infection. Possible hypotheses are discussed--whether a microlesioning effect or a disease-modifying effect of STN-DBS, though neither adequately explain this phenomenon.

Recurrent thunderclap headaches and multilobar intracerebral haemorrhages: two cases of reversible cerebral vasoconstriction syndrome (RCVS).

We describe two patients with thunderclap headaches due to reversible cerebral vasoconstriction syndrome (RCVS). The first patient illustrates multilobar intracerebral haemorrhages as an under-appreciated feature of RCVS, and the second illustrates recurrent thunderclap headache (presumed recurrent RCVS) after a long interval of 4 years. These cases demonstrate the spectrum of presentation of RCVS, a clinically under-recognized condition.

Myelopathy but normal MRI: where next?

For most patients presenting with a spinal cord syndrome MR scanning has become the key investigation in establishing the diagnosis. However, myelopathy with normal spinal imaging remains a common clinical conundrum. In this review we discuss the diagnoses to consider for the neurologist presented with a patient with "MR normal myelopathy". We will illustrate this scenario with a series of short cases and consider the further investigation of "MRI normal" myelopathy.

Paraparesis due to syphilitic aortic dissection.

A patient is presented who developed an acute spinal cord infarct with paraparesis and segmental pain but no sensory or sphincter involvement. Investigations revealed an extensive dissecting thoracic aortic aneurysm and positive treponemal serologic findings consistent with tertiary cardiovascular syphilis.

Genomic imprinting and anticipation in idiopathic torsion dystonia.

Idiopathic torsion dystonia (ITD) is a dominantly inherited disorder with variable penetrance and expressivity. Factors affecting the penetrance of the ITD gene have not yet been identified. The present study used four published series of cases to test specific hypotheses regarding factors that could affect the expression of ITD. Among the combined 253 families, transmission of ITD did not depend on either the sex of the affected offspring or that of the transmitting parent. Furthermore, neither the specific type of dystonia manifested, the site at which clinical signs of dystonia first appeared, nor age of onset differed significantly as a function of the gender of the transmitting parent. However, in familial cases of later onset (age > or = 20 years), nearly all involved a transmitting mother. There is evidence for consistency of age of onset within the subset of Jewish families. Although anticipation effects are apparent, sampling bias cannot be ruled out.

Pathological heterogeneity of clinically diagnosed corticobasal degeneration.

Two patients fulfilling suggested clinical diagnostic criteria for corticobasal degeneration (CBD) are presented, who were found at postmortem to have alternative pathological diagnoses not suspected during life, namely, Alzheimer's disease and Pick's disease, respectively. The nosological position of these cases is considered in light of a literature review of previous reports of clinically diagnosed corticobasal degeneration with atypical (not corticobasal degeneration) pathology. Since such phenocopies may be common, we suggest that all clinically diagnosed cases of corticobasal degeneration should initially be labelled as "corticobasal degeneration syndrome" (CBDS) to emphasize that this is a diagnosis based on clinical phenotype, with the term corticobasal degeneration being reserved for the specific neuropathological phenotype, which itself may have a variety of clinical presentations.

Dyskinetic cerebral palsy: a clinical and genetic study.

The clinical features and family histories of 20 adults with dyskinetic cerebral palsy from 20 families were studied. The majority of the patients showed progressive neurological deterioration in adult life. In only three did the condition stabilise by 10 years of age and in seven there was deterioration after the age of 30. Two patients developed a secondary cervical spondylotic myelopathy. Four patients had affected relatives and there were similar proportions of affected parents and siblings. The family data suggest genetic heterogeneity with autosomal recessive and dominant variants. The existence of an X-linked form cannot be excluded, and the demonstration of an increased paternal age effect among single cases suggests that some of these may arise because of fresh dominant genetic mutation.

Parental age, genetic mutation, and cerebral palsy.

Parental age and birth order were studied in 251 patients with cerebral palsy. No parental age or birth order effects were observed in spastic quadriplegia or diplegia, but a paternal age effect was detected in those with athetoid/dystonic cerebral palsy and congenital hemiplegia. These observations indicate that some cases of athetoid/dystonic or hemiplegic cerebral palsy might arise by fresh dominant genetic mutation.

A case-control study of idiopathic torsion dystonia.

A study of 71 patients with idiopathic torsion dystonia (ITD) and 71 matched controls was performed to investigate the range of possible clinical expression of ITD and the role of environmental factors in the development of the disease. A family history of tremor and stuttering were the only factors significantly associated with ITD. No associated environmental factor was identified.

Intrafamilial correlation in idiopathic torsion dystonia.

Age of onset and severity of idiopathic torsion dystonia (ITD) were studied in 100 British families containing 107 index cases and 79 secondary cases. Analysis of variance of these clinical features did not suggest that ITD is genetically heterogenous, and they were similar in Jewish and non-Jewish patients. Intrafamilial correlation for age of onset was low, particularly between parents and their offspring, suggesting that the ITD phenotype may be determined in part by nongenetic factors or an allelic modifying gene.

Central nervous system haemangioblastoma: a clinical and genetic study of 52 cases.

Fifty two cases of haemangioblastoma were reviewed for their clinical, genetic and prognostic features. Of 34 patients with apparently isolated cerebellar lesions, postoperative outcome was good in 79%. Six isolated spinal lesions presented more insidiously and morbidity was related to incomplete resection. Twelve (23%) of the patients definitely had von Hippel-Lindau disease (VHLD). The true proportion may be higher as this diagnosis was not definitely excluded in many of the remainder; only ten patients with seemingly isolated cerebellar tumours were appropriately investigated and two had evidence of VHLD. Four out of 26 cases (15%) with apparently completely resected, isolated, cerebellar lesions later developed recurrent tumours. Brainstem and supratentorial haemangioblastomas were rare and were always associated with VHLD. The cerebellar or spinal haemangioblastomas due to VHLD had no distinctive clinical features compared with isolated tumours and there was considerable overlap in age of onset between the two groups of cases. All patients with an apparently isolated CNS haemangioblastoma should be investigated for evidence of von Hippel-Lindau disease.

A genetic study of idiopathic torsion dystonia in the United Kingdom.

The inheritance of idiopathic torsion dystonia (ITD) was investigated in 100 British families containing 107 index cases with generalized, multifocal or segmental dystonia, and 79 secondary cases. Fifty-eight index cases had affected relatives, usually in two or more generations. Nearly half of the secondary cases were asymptomatic. Paternal age was increased among the 49 single cases, parental consanguinity was not increased and there was no evidence of genetic heterogeneity. Eleven cases (10.3%) were Jewish, which exceeded the number expected, but they did not differ clinically or genetically from non-Jewish cases. The most likely explanation for the excess of Jewish cases is a founder effect in Eastern Europe. We conclude that, in the UK, approximately 85% of cases of ITD are due to an autosomal dominant gene with about 40% penetrance and highly variable expression, possibly reflecting environmental influences. Approximately 14% of these inherited cases may represent new mutations. The remaining 15% are probably nongenetic phenocopies, but are not clinically distinguishable. There was no evidence in this study for the existence of autosomal recessive or X-linked forms of ITD. The estimated recurrence risk for first degree relatives of familial cases is 21%; the risk is lower for single cases. Of affected individuals, 75% will have developed symptoms or signs of dystonia by the age of 30 yrs.

The relationship between trauma and idiopathic torsion dystonia.

Generalised, multifocal or segmental idiopathic torsion dystonia (ITD), is caused by an autosomal dominant gene with reduced penetrance in about 85% of cases. Of 104 patients with these types of ITD, 17 (16.4%) gave a history which suggested that dystonic movements had been precipitated or exacerbated by trauma. Eight of these 17 patients had affected relatives. If precipitated, dystonia appeared first in the injured part of the body within days or up to 12 months after the trauma and later became more widespread. Peripheral injuries may influence basal ganglia function and provoke the onset of dystonic movements in individuals who are ITD gene carriers.

Degenerative cerebellar ataxia and focal dystonia.

Eight patients with a variety of degenerative cerebellar ataxias are described in whom focal dystonia was a prominent presenting feature.

Successful treatment of childhood onset symptomatic dystonia with levodopa.

Three patients with childhood onset symptomatic dystonia responded to levodopa. None fulfilled criteria for a diagnosis of "dopa responsive dystonia" (Segawa's disease). One may have had athetoid cerebral palsy for almost 25 years. All obtained dramatic and sustained benefit from levodopa therapy. A therapeutic trial of levodopa is advised in all patients in whom dystonia has developed in childhood or early adult life, regardless of suspected aetiology or duration of symptoms.

A genetic study of idiopathic focal dystonias.

A genetic study of idiopathic focal dystonias was undertaken by examining 153 first-degree relatives of 40 index patients with torticollis (14 patients), other focal cranial dystonias (16 patients), and writer's cramp (10 patients). Nine relatives with dystonia were identified in 6 families; 8 of these had symptoms such as clumsiness or tremor, but none were aware of any dystonia. A further 4 relatives, now decreased, were affected by history. Overall, 25% of index patients had relatives with dystonia. The results of segregation analysis suggested the presence of an autosomal dominant gene or genes with reduced penetrance as a common cause for focal dystonia. Segregation ratios were not significantly different from those ratios observed in generalized or segmental dystonia in the United Kingdom, and it is possible that a single autosomal dominant gene mutation is responsible for inherited dystonia in the majority of patients irrespective of distribution or severity.

Lessons from a remarkable family with dopa-responsive dystonia.

A family is described in which dopa-responsive dystonia affected six members and segregated in an autosomal dominant fashion. Patients either presented in childhood with dystonia of the legs, going to develop parkinsonism and pseudo-pyramidal deficits, or in adult life with parkinsonian tremor and rigidity, with pseudo-pyramidal signs. Remarkably, in the three cases with childhood onset the symptoms and signs of the condition were abolished 36 to 52 years later by small doses of levodopa. No long term side effects of levodopa have appeared after 15 years of treatment.

Trinucleotide (GAA)n repeat expansion in two families with Friedreich's ataxia with retained reflexes.

In occasional families in whom cases of classic Friedreich's ataxia (FRDA) coexist with affected cases with retained reflexes, linkage analysis has shown that both map to the FRDA locus on chromosome 9q13-21.1. A gene X25 has been identified within the critical region of the FRDA locus, and an intronic expanded GAA trinucleotide repeat has been found in most cases of FRDA. We report two further FRDA families in whom some patients with classic FRDA were areflexic whereas others had brisk reflexes. Molecular genetic analysis disclosed an abnormal trinucleotide repeat expansion within intron 1 of the FRDA gene in both phenotypes.