Postmortem findings in a case of variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulfate.

BACKGROUND: A small number of patients with variant Creutzfeldt-Jakob disease (vCJD) have been treated with intraventicular pentosan polysulfate (iPPS) and extended survival has been reported in some cases. To date, there have been no reports on the findings of postmortem examination of the brain in treated patients and the reasons for the extended survival are uncertain. We report on the neuropathological findings in a case of vCJD treated with PPS. METHODS: Data on survival in vCJD is available from information held at the National CJD Research and Surveillance Unit and includes the duration of illness in 176 cases of vCJD, five of which were treated with iPPS. One of these individuals, who received iPPS for 8 years and lived for 105 months, underwent postmortem examination, including neuropathological examination of the brain. RESULTS: The mean survival in vCJD is 17 months, with 40 months the maximum survival in patients not treated with PPS. In the 5 patients treated with PPS survival was 16 months, 45 months, 84 months, 105 months and 114 months. The patient who survived 105 months underwent postmortem examination which confirmed the diagnosis of vCJD and showed severe, but typical, changes, including neuronal loss, astrocytic gliosis and extensive prion protein (PrP) deposition in the brain. The patient was also given PPS for a short period by peripheral infusion and there was limited PrP immunostaining in lymphoreticular tissues such as spleen and appendix. CONCLUSIONS: Treatment with iPPS did not reduce the overall neuropathological changes in the brain. The reduced peripheral immunostaining for PrP may reflect atrophy of these tissues in relation to chronic illness rather than a treatment effect. The reason for the long survival in patients treated with iPPS is unclear, but a treatment effect on the disease process cannot be excluded.

Hashimoto's encephalopathy: a steroid-responsive disorder associated with high anti-thyroid antibody titers--report of 5 cases.

We describe 5 patients with a relapsing encephalopathy in association with Hashimoto's disease and high titers of anti-thyroid antibodies. The presentation is usually with a subacute onset of confusion, alteration in conscious level, and focal or generalized seizures. The relapsing course, association with myoclonus or tremulousness, and episodes of stroke-like deterioration are characteristic features. The long-term prognosis is favorable with steroid therapy, though additional immunosuppressive therapy may be required. Neurologic investigation typically shows a diffusely abnormal EEG, high CSF protein level without pleocytosis, and normal brain CT and cerebral angiogram. Isotope brain scan may show patchy abnormal uptake. Hashimoto's encephalopathy should be recognized as a definite neurologic entity and added to the list of CNS complications of thyroid disease.

HLA and syringomyelia.

The HLA status of 53 patients with syringomyelia was assessed. Forty had an associated Chiari anomaly. A significant increase of HLA-A9 was found. Genetic factors may influence the development of syringomyelia.

Acute posterior multifocal placoid pigment epitheliopathy and sarcoidosis.

We report on a patient with acute posterior multifocal placoid pigment epitheliopathy and sarcoidosis. A review of the literature suggests that sarcoidosis may occur more commonly in this condition than previously suspected.

Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 1200 mg/day) in a Q.I.D. regimen.

Remacemide hydrochloride is a low-affinity, non-competitive N-methyl-D-aspartic acid (NMDA) receptor channel blocker, under investigation in epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of remacemide hydrochloride or placebo, as adjunctive therapy, in 252 adult patients with refractory epilepsy who were already taking up to three antiepileptic drugs (including an enzyme-inducer). Patients were randomized to one of three doses of remacemide hydrochloride (300, 600 or 1200 mg /day) or placebo Q.I.D., for up to 15 weeks. An increasing percentage of responders (defined as a reduction in seizure frequency from baseline of > or =50%) was seen with increasing remacemide hydrochloride dose. At 1200 mg /day, 23% of patients were responders compared with 7% on placebo. This difference was significant (P = 0.016), as was the overall difference between treatments (P = 0.038). Adverse events: dizziness, abnormal gait, gastrointestinal disturbance, somnolence, diplopia and fatigue were mild or moderate in severity. Carbamazepine and phenytoin plasma concentrations were well controlled and maintained within target ranges, with no evidence of improved seizure control due to increases in the concentrations of these drugs. A dose-dependent, significant, increase in responders following adjunctive remacemide hydrochloride compared with placebo was observed. Remacemide hydrochloride was well tolerated.

Delayed encephalopathy following cardiac arrest.

A 46 year old woman suffered a post-operative cardiac arrest associated with prolonged depression of oxygenation and respiration. She made a good initial recovery but one year later insidiously developed symptoms of widespread central nervous system damage compatible with a delayed post-hypoxic encephalopathy. This case is unusual in the length of time between the hypoxic insult and the later deterioration and also illustrates other atypical features of a delayed post-hypoxic syndrome.

Myelopathy in Marfan's syndrome.

A patient with Marfan's syndrome and a myelopathy is reported, and the association of multiple spinal arachnoid cysts noted. It is proposed that the basic connective tissue defect in Marfan's syndrome may predispose to the formation of arachnoid diverticuli and that in this case spinal cord damage was the sequel.

Steroids in multiple sclerosis.

Steroids are widely used in treating the relapse of multiple sclerosis. There is no place for long term steroid therapy of this disease. Current practice is a short course of high dose methylprednisolone which can be repeated after an interval, has proven safety and objectively accelerates recovery.

Lithium neurotoxicity.

The peripheral and central neurotoxic effects of lithium carbonate are illustrated by 4 case histories. Lithium neurotoxicity is likely to be more common than the literature suggests. Neurological sequelae may be irreversible and may be associated with therapeutic serum levels. Prevention may be facilitated by more stringent case selection, EEG and clinical monitoring and the development of improved methods of drug level assessment.

Methylprednisolone therapy in multiple sclerosis: a profile of adverse effects.

A retrospective analysis of 350 treatment courses using high dose pulsed intravenous methylprednisolone for relapses of multiple sclerosis revealed a low number of adverse effects. This study confirms that high dose methylprednisolone is a safe therapeutic option in multiple sclerosis.

Hypothermia in multiple sclerosis.

Five patients with clinically definite multiple sclerosis are reported who presented with acute relapses associated with hypothermia. Repeated episodes of hypothermia were seen in four. Thrombocytopenia was associated with the hypothermia in four patients. Further investigation disclosed a tendency to chronic hypothermia and suggested an altered thermoregulatory set point in one patient, when MRI, endocrine, and autonomic studies failed to localise a lesion in the hypothalamus, but subsequent necropsy showed hypothalamic lesions. In such patients a predisposition to altered thermoregulation may occur due to direct involvement of the hypothalamus or from combined lesions affecting hypothalamic outflow to the brainstem and spinal cord.

Some observations on the pathogenesis of syringomyelia.

The pathogenesis of most cases of syringomyelia remains obscure although a modification of the hydrodynamic theory of Gardner allows a logical surgical approach to treatment. Data are presented confirming a high incidence of traumatic birth in patients with syringomyelia who have a Chiari malformation or basal arachnoiditis, but demonstrating no increase in traumatic birth in patients with the Chiari malformation but no syringomyelia. A traumatic birth may be the factor responsible for creating the potential for syringomyelia in those individuals with the embryological defect of the Chiari anomaly.

Hydrocephalus and tuberculous meningitis in adults.

Hydrocephalus is well recognised as a complication of tuberculous meningitis in childhood. This complication may occur more frequently in the acute stage in adults than has been appreciated. Three cases are described to illustrate this observation. Early recognition and prompt treatment may improve mortality and morbidity at any age.

Epilepsy and employment. A community based survey in an area of high unemployment.

A community based survey was undertaken to assess the work record of patients with epilepsy in an area of high unemployment. One hundred and thirty seven epileptic patients were identified from a population of 23,837 persons of employable age registered with three urban group practices in North East England. The unemployment rate for economically active patients with epilepsy was 46% compared with 19% for an age and sex matched control population (p less than 0.01). Fifty nine per cent of patients with active epilepsy were unemployed. In those with an associated neurological or psychiatric handicap and those who were unskilled manual workers the unemployment rates were 79% and 77%, respectively. Patients with epilepsy were less likely to leave school with qualifications or undergo subsequent training or apprenticeships. They were more likely to be unskilled manual workers, single and living in rented accommodation. In an area of high unemployment patients with epilepsy have disproportionately greater difficulty finding work. High unemployment rates among patients with epilepsy are only one aspect of a spectrum of social and economic disadvantage.

Sign language tics in a prelingually deaf man.

Gilles de la Tourette syndrome is characterized by vocal and motor tics starting in childhood. Vocal tics may be either noises or words, and the vocal language tics may consist of obscenities (coprolalia) and repetitions of speech that has been heard (echolalia). We describe a prelingually deaf man who has the full array of tics seen in Gilles de la Tourette syndrome, but in whom vocal language tics are replaced by equivalent sign language tics. This is, to our knowledge, the first report of sign language tics in a person with prelingual deafness. The implications of this phenomenon for the separation between language and ideas in tics and the equivalence of sign language to spoken language is discussed.

Tizanidine in the treatment of spasticity.

A double-blind crossover trial compared tizanidine with baclofen in 36 patients with spasticity. Tizanidine appeared to reduce lower limb spasticity more effectively and to have fewer side effects, but no statistically significant differences emerged when the two drugs were compared. An additional open study of tizanidine confirmed the beneficial action in a selected minority of patients with spasticity. This drug may have an important role in the management of spasticity, but further studies are required.

Cardiovascular reflexes in syringomyelia.

Cardiovascular reflexes were assessed by simple noninvasive tests in 18 patients with syringomyelia restricted to the spinal cord (syringomyelia) and 22 patients with syringomyelia and brainstem signs (syringobulbia), and the results compared with a control group. Postural hypotension occurred more frequently in patients with bilateral brainstem signs, palatal weakness or vocal cord palsy. Vagal cardiovascular reflexes were disturbed in patients with clinical evidence of involvement of the Xth cranial nerve, and also in those with other brainstem signs. The integrity of the efferent limb of the reflex arc was demonstrated in three patients by testing the heart rate response to intravenous atropine. It was observed that cardiovascular reflexes may be impaired in patients free of symptoms of autonomic dysfunction. These findings may be relevant to the occurrence of sudden death in such patients and to the possible anatomical localization of the defect.