Recurrence of acute disseminated encephalomyelitis at the previously affected brain site.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a usually monophasic demyelinating disorder of the central nervous system. Recurrences pose a diagnostic challenge because they can be overlooked or suggest an alternative diagnosis. OBJECTIVE: To examine the frequency, nature, and outcome of recurrent ADEM. DESIGN: Review of the medical records of patients diagnosed in our institution as having ADEM between January 1, 1983, and May 31, 1998. Recurrences were defined as appearance of new symptoms and signs at least 1 month after the previous episode. RESULTS: Five (24%) of 21 patients with ADEM developed recurrent disease episodes. In all, diagnosis was confirmed by brain biopsy. One patient had 4 disease episodes, 2 had 3, and the other 2 each had 2. Recurrence appeared 1.5 to 32 months after initial presentation and involved the same brain territory in 6 of 9 recurrences in 3 of 5 patients. In 2 patients, recurrences included neuropsychiatric signs. A good response to corticosteroid therapy was observed in 10 of 13 of treated ADEM attacks: in 3 of the 4 treated initial events and in 7 of 9 recurrences. CONCLUSIONS: Recurrent ADEM may be more prevalent than previously recognized. Patients who relapse tend to have more than 1 recurrence that usually involves, clinically and radiologically, a brain territory that was affected before and can simulate a space-occupying lesion that requires histologic diagnosis. Neuropsychiatric features may be the main presentation of a relapse. Since recurrent ADEM is a corticosteroid-responsive condition, awareness and early diagnosis are mandatory.

Treatment of multiple sclerosis with copolymer-1 (Copaxone): implicating mechanisms of Th1 to Th2/Th3 immune-deviation.

The synthetic polypeptide copolymer-1 (Cop-1; Copaxone; Glatiramer Acetate) has been recently approved as an effective treatment in relapsing multiple sclerosis (MS). A large body of evidence demonstrates that Cop-1 induces active suppression of CNS-inflammatory disease in animal models. However, Cop-1-mediated suppressor mechanisms have not yet been elucidated in humans. A 12-month open study following clinical and immunological parameters of ten relapsing MS patients treated with Cop-1 is presented. Relapse rates and disability scores (EDSS) were evaluated prior to and after 12 months of treatment. The immunological parameters assessed prior to and at 3 months' interval during treatment included serum levels of soluble IL-2 receptor (sIL-2R) and IL-10 as well as leukocyte cytokine mRNA expression of TNF alpha, IL-4 and TGF-beta. Copaxone treatment was found to lead to a significant reduction in the mean annual relapse rate (from 1.4 prior to treatment to 0.6 during treatment) and stabilization of disability in 90% of the patients. The treatment was accompanied by an elevation of serum IL-10 levels, suppression of the pro-inflammatory cytokine TNF alpha mRNA, and an elevation of the anti-inflammatory cytokines TGF-beta and IL-4 mRNAs in PBLs. These results suggest that the beneficial clinical effects of Copaxone in MS patients may be attributed to changes in activation of T cell subsets and a shift from Th1 to Th2/Th3 cytokine profile, probably leading to Cop-1-driven mechanisms of bystander suppression.

Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells. Implications for multiple sclerosis autoimmune diseases.

The mechanism(s) of action responsible for the anti-inflammatory effects mediated by interferon (IFN)-beta are still elusive although suggestions include anti-viral effects, the enhancement of natural killer (NK) or suppressor T cell activity and opposition to the effects of inflammatory cytokines. As vascular endothelial cells are active participants in inflammatory and demyelinating processes, we decided to examine the effects of IFN-beta on the expression of major histocompatibility complex (MHC) gene products and intercellular adhesion molecule (ICAM)-1 on human vascular endothelial cells (ECs). Human umbilical ECs demonstrated constitutive expression of ICAM-1 and MHC class I molecules but did not express MHC class II molecules. Basal expression of ICAM-1 molecules was enhanced by TNF alpha and to a lesser extent by IFN-beta, but was not affected by IFN-gamma. MHC class I expression on ECs was enhanced by IFN-beta, IFN-gamma, and tumor necrosis factor (TNF)-alpha. Furthermore, a synergistic effect was observed to combinations of these interacting cytokines. Incubation of ECs with IFN-gamma, but not IFN-beta, induced class II expression in a dose dependent manner. Moreover, co-incubation of ECs with IFN-beta and IFN-gamma resulted in significant down-regulation of class II molecules expression which was directly dependent on IFN-beta concentration. Northern blot analysis of DR alpha and Beta 2-microglobulin mRNA expression suggested that cytokine-mediated regulation of MHC molecules is at the transcriptional level, while modulation of ICAM-1 expression appears to be at the transcriptional as well as post-transcriptional level. Thus, our study demonstrated that IFN-beta and interacting cytokines exert complex immunoregulatory effects on endothelial cells with differential modulatory effects on various cell surface markers. Understanding the biological significance of these immunomodulatory effects mediated by IFN-beta may have important implications for cytokine-based strategies in the treatment of inflammatory and autoimmune diseases.

SPECT diagnosis of Creutzfeld-Jacob disease.

SPECT with 99mTc-HMPAO was performed on a 65-yr-old patient with Creutzfeld-Jacob disease. Cerebral blood flow was heterogeneously decreased throughout the brain, differing from the pattern observed in other common types of dementia. These results suggest that HMPAO-SPECT may provide useful information in the differential diagnosis of dementia, specifically when Creutzfeld-Jacob disease is suspected.

Supratentorial and parafalcial subdural empyema diagnosed by computerized tomography. Case report.

A case is presented in which computerized tomography (CT) demonstrated a supratentorial and parafalcial purulent collection. However, neither carotid angiography nor CT revealed the small scattered pockets of pus that were found over the convexity at operation. The entire subdural space was exposed by a wide craniectomy, permitting adequate subdural drainage and decompression of the brain. It is thought that thorough drainage of the entire subdural space is crucial for the attainment of a successful result in a single-state operation.

The effect of deprenyl treatment on directional and velocity control of arm movement in patients with early stages of Parkinson's disease.

Visual motor control (VMC) of arm movements is disturbed in patients with Parkinson's disease. The effect of antiparkinsonian medications on VMC is unknown. To assess the effect of deprenyl, a monoamine oxidase type B inhibitor, on VMC in the early stages of parkinsonism. Fourteen recently diagnosed, unmedicated patients with primary degenerative parkinsonism, mean age 61.9 +/- 2.8 years, were assessed by a computerized VMC system for tracking and tracing on a sine wave, circle, and square. Score was given for total time of test performance, directional error, arm velocity, and number of interruptions in tracking. All patients performed the first VMC test at baseline, prior to any antiparkinsonian treatment. The second test was performed after a month of treatment with 2.5 mg/d of deprenyl, and the third test was done after an additional month of treatment with 10 mg/d of deprenyl. Results were compared with 15 healthy volunteers with a mean age of 63.1 +/- 1.2 years. Parkinsonian patients performed significantly poorer on the VMC when compared to controls. Tracing was more affected than tracking. Tracing total time was almost twice as long as for controls (p < .0005). Treatment with 2.5 mg/d and 10 mg/d of deprenyl improved performance significantly (p < .05 and p < .005, respectively). Velocity of arm movement was not affected by deprenyl treatment in either dose. Directional control (tracing), severely disturbed in the parkinsonian group, improved back to the performance of healthy controls after 10 mg/d of deprenyl. In recently diagnosed parkinsonian patients internally guided VMC tasks were disturbed more than externally guided ones. Deprenyl treatment selectively improved directional control of arm movement in a dose related manner.

Tetrabenazine treatment in movement disorders.

Tetrabenazine (TBZ) is a catecholamine depletor used for the treatment of a variety of movement disorders. The purpose of this study was to assess the efficacy of TBZ in a retrospective chart review in 3 tertiary care movement disorders centers over long-term treatment. Of 150 patients to whom TBZ was prescribed, 118 were followed up and assessed using the Clinical Global Impression of Change (CGIC), (-3 to +3), a composite grade from a patient and caregiver scale over variable periods. The patients had a variety of hyperkinetic movement disorders including dystonia (generalized and focal: axial, Meige syndrome, torticollis, blepharospasm, bruxism), Huntington disease (HD) or other choreas, tardive dyskinesia (TD) or akathisia, and Tourette syndrome. Mean patient age was 48.8 +/- 18.7 years; 48 were men (40.7%) with a mean disease duration of 93 months. The mean follow-up time was 22 months and the mean TBZ dose was 76.2 +/- 22.5 mg/d (median 75 mg, range 25-175 mg/d). The mean CGIC score was +1 (mild improvement). The group of patients who scored +3 on the CGIC (very good improvement) represented 18.6% (n = 22) of all patients. They had HD or other types of chorea 7.6% (n = 9), facial dystonia/dyskinesia (n = 7, 5.9%), 1 with TD, 2 with trunk dystonia, 2 with Tourette syndrome, and 1 with tardive akathisia. This group had the longest treatment duration and received a mean TBZ dose of 70.5 mg/d (median 75 mg/d) for a mean of 25.4 +/- 21.3 months. The report concludes that TBZ is a moderately effective treatment of a large variety of hyperkinetic movement disorders, with excellent effects in a subgroup with chorea and facial dystonia/dyskinesias.

L-DOPA improves visuo-motor coordination in stable Parkinson's disease patients.

The visuo-motor coordination of 26 stable, treated, Parkinson's disease (PD) patients with average Hoehn and Yahr rating of 1.75+/-0.6, was assessed by use of several tracing and tracking tests before and 30min after ingestion of the mid-day levodopa (L-DOPA) dose. Significant improvement was found in all aspects of visuo-motor coordination 30min after drug intake. This included the ability to control the direction and velocity of hand-movement, and the capacity to persist in tracking. A subgroup of 12 patients was tested 30min and 1h after L-DOPA intake. A continuing (but small) improvement in directional and velocity control could still be seen an hour after drug intake, while tracking persistence remained unchanged with respect to the preceding test. We conclude that changes in executional capabilities can be documented in "stable" PD patients, consequent to L-DOPA intake, when high-level skills, such as visuo-motor coordination, are tested.

Tryptophan toxicity--time and dose response in rats.

UNLABELLED: During the past decade L-tryptophan (Trp) ingestion have been associated with a multisystemic syndrome, known as eosinophilia myalgia syndrome (EMS). Even though an epidemic studies indicated that a contaminant, 1,1'-ethylidene-bis-L-tryptophan was involved in EMS, abnormalities in metabolism of Trp have been reported in other similar clinical syndromes such as carcinoid syndrome, scleroderma or eosinophilic fasciitis. The purpose of the study was to investigate the role of Trp or its metabolite, given in different dosing regimens in induction of tissue damage. METHOD: 3 months old female rats (Charles River CD-1) were fed for 3, 6, 12 weeks on a diet containing 20% protein diet derived from casein and supplemented with 1%, 2%, or 5% Trp. On the last week of feeding, half of the animals fed on a control diet and half of the animals fed on the Trp diet were injected with 2 injections of para-chlorophenyl alanine (p-CPA), a Trp hydroxylase inhibitor, 300 mg/kg i.p. followed by 3 injection of 100 mg/kg every alternate day. RESULTS: Body weight of rats fed higher levels of Trp increased slowly and injection of p-CPA induced loss in body weight. 2/6 of the animals treated with 1% Trp and 1/6 treated with 5% Trp for 3 weeks and 2/4 animals treated with 1% Trp and 1/4 treated with 5% Trp for 12 weeks died after injection of p-CPA. No mortality was detected in 1-5% Trp treated animals. Alopecia and skin changes were seen after p-CPA in 1-5% Trp treated animals. Increased amounts of connective tissue and induction of inflammatory cell proliferation were observed in lung, spleen and in gastrocnemia muscle of rats treated with higher dose of Trp for longer period. Induction of kynurenine pathway by injection of p-CPA caused more tissue damage. It is concluded that excessive Trp or elevation of its metabolites could play a role in amplifying some of pathological features of EMS. This pathological damage is further augmented by metabolites of the kynurenine pathway.

[Botulinum toxin injection effective for post-peripheral facial nerve palsy synkinesis].

Facial synkinesis is an involuntary activation of muscles innervated by the zygomatic or mandibular branch of the facial nerve in conjunction with voluntary activation of the other branch. It appears frequently after recovery from peripheral facial nerve paralysis. We report 10 patients with facial synkinesis following Bell's palsy with a mean duration of synkinesis of 7 +/- 4 years before treatment with periorbital injections of Botulinum toxin type A. 9 had marked subjective and objective improvement starting a few days after injection and lasting 4-9 months. The results suggest a useful treatment option for post-Bell's palsy facial synkinesis with Botulinum toxin type A.

[Botulinum toxin for palatal myoclonus and spastic dysphonia].

Botulinum toxin (B; Botox), produced by the anaerobic bacterium Clostridium botulinum, causes temporary paralysis by blocking the presynaptic release of acetylcholine at the neuromuscular junction. This action is clinically used to alleviate muscle spasm by injecting the toxin directly into the overactive muscle. We report our experience with B injections in 2 women, aged 20 and 21, respectively, 1 of whom had bilateral palatal myoclonus and the other adductor spastic dysphonia. Both showed remarkable improvement of conditions for which, until now, we had no effective treatment. These are the first cases in Israel treated with B for otorhinolaryngological conditions.

Effect of ropinirole on visuo-motor test in newly diagnosed Parkinson's disease patients.

OBJECTIVES: The aim of this study was to assess the sensitivity of the visuo-motor test (VMT) compared with the Unified Parkinson's Disease Rating Scale (UPDRS) in newly diagnosed Parkinson's disease (PD) patients. METHODS: VMT and UPDRS were carried out in 20 patients before treatment onset, 2 weeks after treatment with ropinirole 1.5 mg/day and 2 weeks following increasing the dose of ropinirole to 3.0 mg/day. RESULTS: Improvement in clinical status was seen in all patients, with a mean UPDRS reduction of 16.6% following treatment with ropinirole 1.5 mg/day, and 38.9% reduction in UPDRS observed with ropinirole 3.0 mg/day. Initial improvement was not correlated with severity of PD, although further improvement with ropinirole 3.0 mg/day correlated linearly with patient's baseline UPDRS. Improvement in the ability to control the direction of the moving hand during tracing is expressed by the reduction of VMT variables following treatment. Mean VMT variables were 36.2% at baseline, 34.0% with ropinirole 1.5 mg/day and 31.7% with ropinirole 3.0 mg/day. Although changes in VMT variables were less uniform across patients, on average, it did correlate with patients UPDRS. CONCLUSIONS: We suggest that VMT can be useful in the assessment of treatment effect on high-level motor planning and cognitive capabilities in newly diagnosed PD patients, added to the UPDRS which does not appropriately comply with those skills.

Superficial hemosiderosis of the central nervous system.

Superficial hemosiderosis (SH) of the CNS is a rare disease caused by repeated subarachnoid hemorrhage, with progressive superficial siderosis of the CNS. We report a patient with SH whose clinical picture was marked by progressive gait ataxia, hearing loss, dysarthria, and recurrent episodes of hemifacial spasm. Iron and ferritin levels in the CSF were significantly higher than in a control group of patients. Six month's treatment with the iron-chelating agent trientine dihydrochloride led to clinical improvement, with a concomitant reduction of CSF iron level. We suggest that, in addition to magnetic resonance imaging findings, CSF levels of iron and ferritin should be used as diagnostic criteria for SH, as well as to estimate the efficacy of iron chelation treatment.

Sphenoid sinusitis presenting as chronic meningitis.

Sphenoid sinusitis is a frequently misdiagnosed infection. Delay in recognition and treatment carries a very poor prognosis. An unusual case of sphenoid sinusitis mimicking a syndrome of chronic meningitis is presented. This case emphasizes the diagnostic challenge of sphenoid sinusitis which may present only through its complications.

Normal-pressure hydrocephalus associated with spinal cord tumor.

While the association of spinal cord tumor and high-pressure hydrocephalus is well known, only 5 cases of spinal cord tumor associated with normotensive hydrocephalus have been reported. Two further cases are described here, discussing the possible pathophysiological mechanism. It is suggested that these patients go through a subclinical stage of high-pressure hydrocephalus and become normotensive later on, a process which might influence the surgical results.

Long-term remission of idiopathic cervical dystonia after treatment with botulinum toxin.

Botulinum toxin type A (BTX-A) treatment for cervical dystonia is traditionally considered a purely symptomatic treatment. BTX-A blocks acetyl choline exocytosis for 3-6 months and most patients require reinjection after this period. We report on 6 patients (mean age 41.6 years, range 18-69) with idiopathic cervical dystonia who were treated with BTX-A injections and became asymptomatic for 2-4 years. Four patients showed remission after the first BTX-A treatment, 1 patient after the second set of injections and 1 after the third session. Amelioration of neck dystonia was observed within 1-4 weeks after the last BTX-A treatment and all 6 patients are symptom-free, off antidystonic medications for over 2 years. The possibility that BTX-A treatment may increase the chances of development of clinical remission in patients with idiopathic cervical dystonia is discussed.

Interventional neurology: botulinum toxin as a potent symptomatic treatment in neurology.

Local injections of botulinum toxin is a well-accepted treatment for focal dystonias, hemifacial spasms and strabismus. Its use by skilled neurologists has been reported to be safe and effective. We report our experience with botulinum toxin injections in 108 patients with various central nervous system disorders. Botox was effective in upper face dystonia (86% improvement), spastic dysphonia (92% improvement), platysma muscle spasms and spasmodic torticollis (range of movement 61%, pain and tension 90%). It was also very effective in a few patients with apraxia of eyelid opening, parkinsonian jaw tremor, teeth clenching, palatal myoclonus and adductor leg spasticity. No serious side effects were recorded. Botulinum toxin is a useful symptomatic treatment for many neurological disorders, and one of the leading mode of treatments in the new subspecialty in neurology called "Interventional neurology."

The role of botulinum toxin in the treatment of lower limb spasticity in children with cerebral palsy--a pilot study.

The use of botulinum toxin in cerebral palsy is still experimental. We conducted a pilot clinical trial with botulinum toxin injections on 14 children with spastic cerebral palsy. All patients were mobile with dynamic contractures of the gastrocnemius-soleus muscles. The injections were monophasic in 9 patients and biphasic in 5 patients. Improvement in dorsiflexion, quality of gait and grade of independence were achieved in 3 patients; improvement in dorsilflexion and quality of gait were achieved in 6 patients. There was no significant change in quality of gait in 4 patients. The beneficial effect lasted 4-9 months (mean 6.7 months). A combined functional score given by the physicians, therapists and parents showed a marked improvement in 6 patients (42.9%), a mild improvement in 3 patients (21.4%) and no improvement in 5 patients (35.7%). Biphasic injections were slightly more effective than monophasic injections (p < 0.02). Adverse effects were usually mild. We conclude that botulinum toxin may be used for the reduction of spasticity in patients with cerebral palsy who have dynamic deformities of the ankle joints.