CACNA1A R1347Q: a frequent recurrent mutation in hemiplegic migraine.

Of the 18 missense mutations in the CACNA1A gene, which are associated with familial hemiplegic migraine type 1 (FHM1), only mutations S218L, R583Q and T666M were identified in more than two independent families. Including the four novel families presented here, of which two represent de novo cases, the R1347Q mutation has now been identified in six families. A genotype-phenotype comparison of R1347Q mutation carriers revealed a wide clinical spectrum ranging from (trauma triggered) hemiplegic migraine with and without ataxia, loss of consciousness and epilepsy. R1347Q is the third most frequent mutation in hemiplegic migraine patients and should therefore be screened with priority for confirmation of clinical diagnosis. This study clearly demonstrates that the availability of multiple families better reflects the full clinical spectrum associated with FHM1 mutations.

Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs phenytoin.

OBJECTIVE: To evaluate the efficacy and tolerability of the treatment with valproic acid (VPA) in patients with status epilepticus (SE) or acute repetitive seizures (ARS) comparing it with phenytoin (PHT) treatment. MATERIALS AND METHODS: Patients with SE or ARS were treated in a consecutive manner with either VPA or PHT intravenously. The primary endpoint was defined as clinical seizure cessation; the secondary endpoint was evaluation of drug tolerability. RESULTS: Seventy-four adult patients with SE or ARS participated in the study, 49 with VPA i.v. and 25 PHT i.v. In 43 (87.8%) of the VPA patients, the seizures discontinued, and no rescue medication was needed. Similar results were found in the PHT group in which seizures of 22 (88%) patients were well controlled. Side effects were found in 12% of the PHT group, and in none of the VPA group. CONCLUSIONS: VPA i.v. seems to be effective and well tolerated in adult patients with SE or ARS.

Severe diffuse systemic amyloidosis with involvement of the pharynx, larynx, and trachea: CT and MR findings.

Amyloidosis is a term applied to a diverse group of disorders that share the deposition of amyloid protein in various extracellular tissues. Systemic amyloidosis may involve almost any organ system in the body including regions in the head and neck; however, pharyngeal involvement is rare, with only 12 cases having been previously reported. Ten of these cases were localized disease, and only 2 cases were systemic amyloidosis. We present the case of a patient with severe diffuse systemic amyloidosis with extensive involvement of the pharynx, larynx, trachea, lungs, eyelids, and breasts. We also review the imaging characteristics and pertinent literature.

Migrating subdural hematoma without subarachnoid hemorrhage in the case of a patient with a ruptured aneurysm in the intrasellar anterior communicating artery.

Acute spontaneous subdural hematoma without the presence of a subarachnoid hemorrhage as a result of a ruptured aneurysm is rare. We present the case of a patient with an aneurysm of the intrasellar anterior communicating artery that caused hemorrhage solely into the subdural space. The hemorrhage then migrated down the spinal canal. Our case is unique because all these 3 rare processes occurred in a single patient. Identification of the cause of this type of hemorrhage in a timely fashion is crucial to the management of such a patient.

Cervical paraspinal electromyography: normal values in 100 control subjects.

The normal electromyographic values and the significance of spontaneous activity, when examining the cervical paraspinal muscles, has been studied rarely, and there are very few studies concerning this issue. To obtain muscle unit potential (MUP) reference values for cervical paraspinal muscles, we examined 100 volunteers. Spontaneous activity and the analysis of 20 MUPs in every individual were checked by the automated MUP analysis program. In those individuals ages 20 to 40 years, no spontaneous activity was observed, and in the ones ages 40 to 60 years and 60 years or older, fibrillations and/or positive sharp waves were seen in 8% and 92%, respectively. MUP values were found to be close to those of upper limb muscles. Age has no significant effect on MUP values, except for mean amplitude that was increased in individuals ages 60 to 80 years.Our findings suggest that fibrillations and positive sharp waves do not have much electrodiagnostic value in the study of cervical paraspinal muscles of middle-aged and elderly subjects, when it is an isolated finding, and there is a need for an extended electromyographic examination, including other muscles, to exclude radiculopathy. Automated MUP analysis is easily performed, and our results may serve as reference values.

Early treatment of a single generalized tonic-clonic seizure to prevent recurrence.

BACKGROUND: The question of whether to start antiepileptic treatment after a single unprovoked seizure remains controversial and has been the subject of much debate in the relevant literature. OBJECTIVES: To determine the rate of recurrence of a second attack after a single unprovoked epileptic seizure by using 2 study groups of treated and untreated patients and, thus, to establish a treatment policy for these patients. PATIENTS AND METHODS: A group of 91 patients with a single generalized tonic-clonic seizure were prospectively studied; 87 of these patients completed the study. The end point of the study was 36 months after the single attack or the occurrence of a subsequent epileptic attack. The patients were randomly divided into 2 groups; 45 patients who immediately received anticonvulsive treatment and 42 who remained untreated for the follow-up period. Patients in the treated group were given monotherapy with carbamazepine. The results of recurrences were statistically analyzed by using the Kaplan-Meier method. RESULTS: Results indicated a significantly higher percentage of seizure-free patients in the treated group compared with that in the untreated group (P = .001). The treated men were proved to be less at risk for recurrent seizures compared with treated women (P < .001 vs P = .03, respectively). CONCLUSION: Treatment after a single unprovoked seizure leads to a significant reduction in the risk of relapse of generalized tonic-clonic epilepsy.

Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis.

Ten patients with relapsing-remitting multiple sclerosis were treated with intravenous immune globulin, 0.4 g/kg per day for 5 consecutive days, and then with additional booster doses of immune globulin of 0.4 g/kg, once every 2 months, for the next 12 months. Ten untreated patients with relapsing-remitting multiple sclerosis who were matched with the study patients for age, disease duration, and number of attacks per year served as controls. Immune globulin treatment was well tolerated, with no side effects. The exacerbation rate decreased from 3.7 +/- 1.2 exacerbations per year before treatment to 1.0 +/- 0.7 exacerbations per year during the treatment in the immune globulin-treated patients, while it remained unaltered in the controls. The posttreatment Kurtzke Expanded Disability Status Scale score decreased from a mean of 4.45 to 4.15, whereas in controls it increased from 3.55 to 3.75. The results suggest that immune globulin suppresses the ongoing pathologic process in multiple sclerosis and may be a promising treatment to prevent disease exacerbations.

Selective acalculia with sparing of the subtraction process in a patient with left parietotemporal hemorrhage.

We describe a patient with left parietotemporal hemorrhage with selective acalculia for addition, multiplication, and division, but with an intact ability to subtract. There was no impairment in the ability to distinguish mathematical signs. This case suggests that different processing systems are responsible for each of the basic arithmetic operations.

Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses.

We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS.

Anterior operculum syndrome localized by SPECT.

UNLABELLED: The aim of this case report was to present a patient with complete anarthria and orofacial apraxia without other relevant neurological deficit. The clinical features are compatible with anterior operculum syndrome. METHODS: A regional brain perfusion scan was done using 99mTc-HMPAO and a SPECT gamma camera. A brain CT scan and an MRI were also performed. RESULTS: Brain CT and MRI were not diagnostic. On brain SPECT, hypoperfusion of the left inferior area of the frontal lobe was noted. CONCLUSION: The patient studied showed an uncommon case of anterior operculum syndrome of focal degenerative origin localized by SPECT. SPECT may be a useful and effective method for diagnosis of this unusual neurological deficit.

Cerebrospinal fluid magnesium level as a prognostic factor in ischaemic stroke.

Magnesium has been reported to have a dilatatory effect on cerebral arteries. Reduction of extracellular Mg+2 has been shown to be directly correlated with the intensity of cerebral spasm. A neuroprotective effect of magnesium in stroke has also been hypothesized. The aim of our study was to examine the Mg+2 levels in serum and cerebrospinal fluid (CSF) in the early stage of stroke and to evaluate the correlation between Mg+2 levels and the development of neurological deficits. Between 1986 and 1994, 96 patients who had a stroke of 24- to 48-h duration were enrolled in the study. Serum and CSF levels of magnesium were checked on admission, 2448 h after the onset of stroke. Using a neurological score, the neurological deficit was assessed on the 1st day, 1 and 4 weeks later. Computed tomography (CT) was performed after 1 week, and the volume and location of infarction were calculated and measured. Statistical analysis was performed for cortical and subcortical patients separately, using Spearman correlation and multiple linear and logistic regression analyses. Significant correlation was found between CSF Mg+2 and the size of the infarct (P < 0.0001). There was no correlation between serum Mg+2 and CSF Mg+2 levels. Regression analysis demonstrated an increase in the values of the Mathew Neurological Score with higher CSF Mg+2 levels. This association remained true after other factors such as age, associated heart disease, diabetes and infarction size had been taken into account by the regression model. The results confirm that there is a relationship between a low Mg+2 concentration in CSF during the first 48 h after onset of ischaemic stroke and the intensity of the neurological deficit. The therapeutic consequence of this finding may have some importance.

Rhabdomyolysis induced by simvastatin and ketoconazole treatment.

Rhabdomyolysis is described as an adverse event of simvastatin therapy either by itself or in combination with other medications. It is unclear whether this phenomenon is specific to simvastatin or to all cholesterol-lowering agents as single-dose therapy or caused by the association of special coadministered medications. We describe two cases in which rhabdomyolysis developed after coadministration of simvastatin (20 mg/d) and the antifungal ketoconazole. The clinical features, blood examination results, and positive outcome were very similar in both cases. We concluded that ketoconazole, an antifungal sterol synthetic inhibitor of the azol group, may induce rhabdomyolysis in patients undergoing treatment with simvastatin, a lipid lowering agent, and increase the possibility of muscle-damaging adverse events of the agents.

Intravenous administration of magnesium sulfate in acute stroke: a randomized double-blind study.

A randomized, placebo-controlled, double-blind study was performed as a pilot study to examine the benefit of the administration of magnesium sulfate given intravenously as a protective substance during the first 24 hours following a stroke. Patients who had cortical infarction in the middle cerebral artery territory with moderate to severe neurologic deficits lasting for more than 15 minutes with onset less than 24 hours were included. The patients were treated with magnesium sulfate or placebo for 5 days and examined by a blinded investigator. Patients had follow-up for 30 days. The primary efficacy variable was the proportion of patients reaching mild to moderate neurologic deficit on the Orgogozo scale (80 points) and relative functional independence on the Barthel index (60 points). Orgogozo scale and Mathew scale values were obtained on admission and days 2, 4, 8, and 30 after stroke. Barthel activities of daily living index and Rankin disability score were obtained on day 30. Forty-one patients (22 given treatment and 19 given placebo) demonstrated significant beneficial effects on the Orgogozo scale (84 +/- 11 vs. 64 +/- 10, p < 0.0001) and (83 +/- 14 vs. 70 +/- 15, p < 0.009), respectively. At the end of 1-month follow-up, the Barthel ADL index was nonsignificantly higher and the Rankin disability score was marginally significantly lower in the magnesium-treated group (84 +/- 26 vs. 71.8 +/- 26, p < 0.143) than in control subjects (2.3 +/- 1.1 vs. 3 +/- 1.3, p < 0.077). Intravenous magnesium sulfate had significant positive effect on the outcome in patients with acute stroke. Further studies on a larger scale are needed to confirm these findings.

Bilateral ptosis and changes in state of alertness in thalamic infarction.

Uni- or bilateral supranuclear ptosis is known to be caused by cerebral lesion. The exact anatomical cortical and subcortical basis is still undefined. We report a case of a patient developing bilateral ptosis with a left thalamic lesion. The bilateral ptosis was associated with transient changes in the state of alertness. We postulate that the thalamus, especially the anterior region, may have an influential role on the pathway from the cortex via the posterior branch of the internal capsule to the levator palpebrae superioris nuclei.

Familial dyslexia associated with cavum vergae.

Three members of one family, diagnosed as dyslexic, are described. All of them have variations of midline cavity: cavum vergae or cavum septum pellucidum, diagnosed by neuroradiological examination. In contrast, the non dyslexic members of the same family have no neuroanatomical congenital variations. We raise the possibility of a functional correlation between the dyslexia and the anatomical findings in the affected members of this family.

Strokes mimicking peripheral nerve lesions.

Sensory-motor deficit in a peripheral nerve pattern due to brain lesion is rarely documented. We report on seven patients with a clinical manifestation of sensory-motor deficit, imitating peripheral nerve involvement, due to lacunar brain infarcts verified by brain computed tomography scan. Five of the patients had an ulnar nerve-like deficit and two median nerve-like deficits. The infarcts were located in the thalamus and the corona radiata. No clinical or electrophysiological evidence for peripheral nerve involvement was found. The unusual peripheral nerve pattern of lesions caused by lacunar brain infarcts can be defined as an additional lacunar syndrome and must be taken into consideration in the clinical evaluation of peripheral nerve deficits with normal nerve conduction velocity.

Laboral outcome after acute unilateral vestibulopathy.

Sixty-five adult patients who had acute peripheral vestibulopathy (APV) were followed-up to determine their functional outcome. During the acute phase, they were treated with betahistine and mobilization. In the entire study population, APV was not significantly associated with a change in occupational activities, physical work or driving ability. Older individuals had significantly attributed a change in work to disease other than APV. Change attributed to APV occurred significantly more frequently in women than in men. The therapeutic approach seems beneficial.

[Complications of low-dose amiodarone].

Complications of low-dose amiodarone in 83 patients, in whom the drug was effective and who were followed for 1-13 years, are presented. Hypothyroidism was diagnosed in 11 (in 8 by the finding of elevated TSH). In 2 of the 3 in whom clinical signs of hypothyroidism were evident, amiodarone was continued, but thyroxine was also given. In 5 others thyrotoxicosis ensued. Propylthiouracil (PTU) was given and amiodarone was discontinued. PTU was then stopped within 4-8 months, without recurrence of the hyperthyroidism. In 1 patient pneumonitis resolved spontaneously a few weeks after stopping amiodarone. Because of gastrointestinal distress amiodarone was stopped in 1 patient. In none were liver enzymes elevated, nor was the nervous system affected clinically. Photosensitivity in 6 patients and skin discoloration in 2 did not necessitate discontinuation of the drug. Blurred vision was reported by 4, but its connection with amiodarone was not proven. There was sinus bradycardia in 2. There was no arrhythmic effect of amiodarone seen on ECG nor on Holter monitoring, nor was there any mortality. We conclude that amiodarone in low doses causes many complications, most of them mild and transient. However, in only a few cases is discontinuation of the drug indicated.

[Effect of low-dose amiodarone on thyroid function].

Thyroid function was examined periodically in a group of 85 patients treated with low-dose amiodarone, and followed for 1-13 years (mean 3.6). Biochemical hypothyroidism (elevated thyroid stimulating hormone (TSH) only) developed in 8 patients and clinical hypothyroidism in 3, while hypothyroidism developed in 5. In the first 11 cases amiodarone was continued but 1-thyroxine was added. In the 5 that became hyperthyroid, amiodarone was stopped and thyroid function became normal within a few months. In the 69 patients without thyroid dysfunction, elevated thyroxine (T4) and free thyroxine index (FTI) were found in 20% and 17%, respectively, and elevated free T4 (FT4) in 28%; all had normal total tri-iodothyronine (TT3) and TSH. In practically all patients, reverse T3 (rT3) rose more than 30% above initial levels. It is concluded that in patients treated with low dose amiodarone: 1) thyroid function should be followed closely; 2) elevated levels of TT4, FTI and FT4 do not necessarily imply hyperthyroidism; 3) hypothyroidism may be biochemical only, without progression to overt hypothyroidism, despite continued treatment; 4) both the hypo- and the hyperthyroidism induced are usually reversible; 5) amiodarone may be continued despite onset of hypothyroidism, provided replacement therapy is given.