Murat Alemdar

Does metoprolol inhibit the cortical spreading depression? Acute effects of systematic metropol on CSD in rats

Cortical spreading depression (CSD) is supposed to be the underlying biological basis of the migraine aura. Metoprolol was proven to be effective in migraine prophylaxis in clinical trials, but its mechanism of action has not been clarified yet. We studied direct effects of metoprolol on a continuous CSD induction model in rats. Six adult Wistar rats were anaesthetized with intraperitoneal thiopental (50 mg/kg). CSD was induced with application of 1 M KCL through a burr hole into the left frontal dura-mater, and recorded by an Ag/AgCl DC electrode on the left parietal dura-mater. After a basal recording of CSD induction during the first 40-min period, metoprolol (5 mg/kg) was infused within 4 min. Then DC recordings were maintained for a further 120 min. Any significant differences in total number and duration of CSDs before and after metoprolol administration were not detected. This study suggests that the mode of action of metoprolol in prophylaxis is not via direct CSD inhibition.

Limbic encephalitis presenting with anxiety and depression: a comprehensive neuropsychological formulation.

Limbic encephalitis (LE) is a paraneoplastic neurological disorder in which, typically, the neurological symptoms occur before the cancer is diagnosed. We report on a 52-year-old male with LE who has depressive and anxiety symptoms. Cranial MRI revealed increased hippocampal signal intensities in both temporal lobes. Extensive range of symptoms concerning emotion, personality and social functioning was assessed with a comprehensive neuropsychological formulation. The neuropsychological test battery showed dysfunction of hippocampus, medial temporal lobes, limbic system and frontal diencephalic structures. The current literature about the neurological mechanisms underlying the neuropsychological findings of LE is also briefly reviewed in this report.

Tremor in idiopathic distal acquired demyelinating symmetric neuropathy.

Recently, the journal Movement Disorders published a study1 that suggested pathological lesions in essential tremor might be distributed similarly in each cerebellar cortex and two case reports that included important suggestions that the successful treatment strategies in tremor associated with paraproteinemic neuropathy might act to modify the abnormal activation patterns in the cerebellar functional system.2,3 We report on a 71-year-old man with distal acquired demyelinating symmetric (DADS) neuropathy who had complaints of gradually increased weakness and clumsiness in his extremities symmetrically for 5 years. A disabling tremor had been seen in his right hand 4 years ago and in the left hand after 6 months. He had not received any medical treatment for these complaints. No history of a central nervous system (CNS) disorder, familial neuropathy, or essential tremor were present. Neurological examination revealed mild distal muscle weakness, areflexia, severe sensory loss in glove and stocking distribution, imbalance, and sensorial ataxia. Postural and action tremors were observed predominantly in the distal muscle of upper extremities. He had no significant leg tremor or any sign of Parkinson’s disease. Findings in electrophysiological studies were consistent with mixed motor–sensory but predominantly sensory demyelinating axonal polyneuropathy. Slowing in conduction velocity of median (48 m/sec in right), ulnar (40.2 m/sec in right), and posterior tibial (26.4 m/sec in right) motor nerves was detected. Sensory nerve action potentials of sural, superficial peroneal, ulnar, and median nerves, and motor nerve action potential of peroneal nerve were absent. Sural nerve biopsy demonstrated a mild decrease in the number of myelinated nerve fibers and severe axonal involvement. Surface electromyogram recordings revealed a rhythmic and synchronous activity of the wrist extensor and flexor muscles (frequency, 6.5 Hz in right hand) during antigravity posture maintenance. Routine laboratory findings, bone marrow examination, and computed tomography scan of the brain were completely normal. Protein concentration was elevated in the cerebrospinal fluid (46 mg/dl). Serum protein and immunofixation electrophoresis were normal. The level of antibodies reactive to myelin-associated glycoprotein (anti-MAG Ab) examined with thin-layer chromatography, enzyme-linked immunosorbent assay, and Western blot analysis (titer, 1:1,600) was also normal. Prednisone was given at an initial dose of 1 mg/kg per day and gradually tapered to 0.5 mg/kg per day after 4 months. But electrophysiological studies did not show any improvement in neuropathy at 6 months. Primidone was started at an initial dose of 125 mg/day and then gradually increased to 500 mg/day. Tremor assessment was quantified using the Fahn–Tolosa– Marin Rating Scale, administered before initiating primidone therapy, on the 15th day, and at the end of the 6th month. A 5-point scale was used, and the maximum possible score was 156 points. The total score was 58 at baseline, 36 at 15 days, and 16 at 6 months. A relevant decrease in tremor amplitude and frequency (4.5 Hz in right hand), and improved skills in assessed tasks (such as pouring and writing) were noticed. He reported significant improvement in activities of daily living without any side effect. Primidone was discontinued at the end of 6 months to evaluate treatment efficacy. Interruption caused a worsening in tremor (score, 52). Treatment was then restarted and resulted in marked improvement (score, 16). DADS neuropathy is an acquired demyelinating polyneuropathy present with distal, symmetric, predominantly sensory or sensorimotor involvement. Nearly two thirds of the patients have an M-protein, usually immunoglobulin M (IgM) kappa monoclonal protein (DADS-M). The remaining one third does not have it, and the condition is referred to as idiopathic DADS neuropathy (DADS-I).4,5 These patients also were categorized on the basis of antibodies reactive to anti-MAG Ab.6 An action or postural tremor prominent in distal muscles of upper extremities is one of the manifestations of peripheral neuropathies.7,8 It may improve with propranolol hydrochloride in dysgammaglobulinemic polyneuropathy, supporting the hypothesis that tremor is due to enhancement of physiologic tremor.7–9 However, most patients reveal relatively higher amplitude, lower frequency, irregular, and asymmetric tremor that improves as the neuropathy responds to immunosuppressive therapy, which is characteristic of neurogenic tremor.9–11 According to neurogenic theory, dispersed and distorted muscle spindle input due to slow peripheral conduction are central to the generation of tremor in demyelinating neuropathies. These inputs subsequently cause a confusion in the CNS generator that is structurally intact but misled into producing tremor. Activation studies using positron emission tomography have also indicated that cerebellar hemispheres appear to be overactive in patients with tremor associated with IgM paraproteinemic neuropathy.12,13 Even though a few publications about the characteristics and treatment of the tremor seen in dysgammaglobulinemic polyneuropathy are present in the literature, only a very limited amount of data is present about the tremor seen in DADS-I neuropathy. In an early study, patients with demyelinating polyneuropathy without anti-MAG Ab were reported to exhibit tremor having the same characteristics with exaggerated physiologic tremor (EPT).9 Our patient exhibited an asymmetric tremor with relatively higher amplitude and lower frequency (4.5–6.5 Hz) than seen in EPT (8–12 Hz).13 Findings in our case and in a previous report on a patient having tremor associated with nonparaproteinemic demyelinating polyneuropathy support the neurogenic mechanism in generation of Published online 19 August 2005 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20693 Movement Disorders Vol. 20, No. 11, 2005, pp. 1529–1530

Isolated abducens nerve palsy associated with retinoic acid therapy: a case report.

Isolated abducens nerve palsy is a rare complication of treatment with various drugs. Here, the authors report the case of a 23-year-old female with isolated left abducens nerve palsy after long-term retinoic acid therapy. The association is based on the temporal relationship and the exclusion of other possible etiologic factors following extensive laboratory and imaging diagnostics. The authors suggest that isolated abducens nerve palsy may be a presenting sign of a toxic neuropathy associated with retinoic acid therapy. After the exclusion of other organic lesions, especially idiopathic intracranial hypertension, and an assessment of the risk-benefit ratio, discontinuation of treatment must be considered in such cases.

Route Learning Impairment Associated with Encephalomalasia Secondary to Traumatic Brain Injury: A Case Report

Topographical disorientation is marked by difficulty finding ones way in familiar or new environments. The present case study reports findings from a 30-year-old male with encephalomalasia of the left parahippocampal region secondary to brain trauma with subsequent difficulty in learning of new routes. His navigation in premorbidly known (familiar) surroundings was intact. Magnetic resonance images revealed left parahippocampal and bilateral occipital encephalomalasia. Neuropsychological screening showed impairment in structuring a representation of the spatial relationships among landmarks with relatively preserved ability to learn visual and verbal information of these landmarks. Decreased visual perception and inappropriate visual inputs due to cervical dystonia and right homonymous hemianopsia also appear to play a role in his disability. The current knowledge about the neuronal systems involved in visual cognition and topographical orientation also are addressed in this report.

The importance of EEG and variability of MRI findings in acute hemorrhagic leukoencephalitis.

Sir, Acute haemorrhagic leukoencephalitis (AHLE) is a lethal haemorrhagic variant of acute disseminated encephalomyelitis (ADEM), a rare demyelinating disorder of central nervous system. A 22-year-old woman was referred to our hospital with status epilepticus. Her seizures were treated with phenytoin infusion. In the next day, neurological examination revealed global aphasia and right-sided hemiplegia. High degree of fever and leukocytosis (22.000/mm) were detected suggesting a preceding infection. Antibiotic and antiviral agents were introduced. Magnetic resonance imaging (MRI) of brain showed large hyperintense areas including some isointense regions on diffusion-weighted signal intensity (DWI). These areas were observed as hypointense on apparent diffusion coefficient (ADC) again including some isointense regions (Fig. 1). T1 and T2-weighted images were completely normal. In spite of mannitol and dexamethasone treatment, total quadriplegia and increased muscle tonus prominent in neck and face muscles were observed during the follow up. Electroencephalogram (EEG) revealed slow background activity and a rhythmic focal delta activity in left hemispheric derivations (Fig. 2). A new MRI scan was performed and large hyperintense lesions scattered in both hemispheres in T1 and T2-weighted images with partial contrast enhancement were detected (Fig. 3). Findings in DWI and ADC mapping were completely reversed. Diagnosis of AHLE was made and 1000 mg/day intravenous methylprednisolone treatment was introduced. All neurological impairments, MRI and EEG findings were resolved within 10 days. Acute disseminated encephalomyelitis typically begins within 6 days to 6 weeks after an infection or vaccination. Long-tract signs and impairment of consciousness are the most common features. Seizures, aphasia and extrapyramidal signs like hemidystonia or rigidity could be occurred infrequently. The diagnosis is usually based on MRI studies. Most common abnormalities are bilateral asymmetric multiple small lesions (<5 mm) and large confluent white matter lesions. AHLE (some degree of

A non-traumatic interhemispheric subdural haematoma: presented with headache as the sole complaint

Due to their localisations and symptoms, interhemispheric subdural haematomas (ISH) compose a distinct category. Altered level of consciousness and hemiparesis are the most frequent symptoms. We report a case of ISH who presented with headache as the sole complaint. Left cerebellar haematoma and ISH were found in cranial MRI and cranial computed tomography Cranial MR angiogram was normal. Haemogram and coagulation parameters were within normal limits. ISH should be considered among the diagnostic possibilities in elderly patients who present with headache as the sole symptom without other clinical features such as meningeal irritation signs, focal neurological symptoms and alteration of consciousness. Cranial imaging studies should be done in such cases.

Short-lasting unilateral neuralgiform headache with severe lacrimation and mild conjunctival injection

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) were first described by Sjaastad et al. (1). It has been accepted as unilateral orbital, supraorbital or temporal or pulsating pain lasting 5–240 s. Pain is accompanied by ipsilateral conjunctival injection and lacrimation. Attacks occur with a frequency from 3 to 200 per day (2). Some clinical features in SUNCT, such as attack duration, pain profile as well as the precipitating mechanisms, are suggestive of a link with first division (V1) trigeminal neuralgia (TN) (3). From a nosological perspective, attacks changing from TN to SUNCT have been reported (4). Sesso (5) suggested that the autonomic features occur just above a ‘certain pain threshold’ and proposed that many cases diagnosed as SUNCT are TN in reality. Sjaastad et al. (6) emphasized that, V1 trigeminal neuralgia resembles to SUNCT only in later stages of the disease, during severe and long-lasting attacks. Even during these attacks, conjunctival injection and lacrimation, hallmarks of SUNCT, are mostly mild. Neurosurgical literature contains many references to atypical TN (7). Some neurosurgeons believe that current concept of the pathophysiology of TN may have been artificially constrained by clinical classification of the disorder (8). A typical form of TN may, in prolonged cases, develop atypical signs. In contrast, many cases of TN start with pain lacking the typical characteristics of TN, and later develop all the hallmark signs of TN (9). In this article, we presented a case with shortlasting unilateral neuralgiform headache attacks which did not fit into classical descriptions of TN and SUNCT. Our main focus was the accompanying autonomic symptoms of attacks; thus, we analysed laterality, timing and degree of each autonomic symptom. Case report

P194 Median-to-ulnar nerve comperative tests in diagnosis carpal tunnel syndrome (CTS)

Purpose: Although production of emotional prosody is a cognitive function of high clinical and social importance, its underlying neural principles are not yet fully understood. The goal of this study was to get an insight into these mechanisms using repetitive transcranial stimulation (rTMS). Method: rTMS was applied over the left and right dorsolateral prefrontal cortex (DLPFC) during two separated sessions using 10 Hz frequency at 100% of resting motor threshold. Three series of stimulation were delivered with ten minutes breaks between first and second series. Each of three 2.5 min series of stimulation consisted of 15 1-s trains with a 10-s between train interval resulting in a total of 450 stimuli delivered. Additionally, sham stimulation was performed by positioning figure 8-shaped coil at the angle of 45° to the skull. After rTMS 16 healthy subjects (8 female) pronounced semantically neutral word “ANNA” in happy, neutral or sad emotional intonation. The fundamental frequency F0 (its mean and modulation) was analyzed and compared between different stimulation conditions. The study was approved by the ethics committee of the Hanover Medical School. Results: Analysis of volitional speech showed statistically significant difference (p<0.05) and reduced mean F0from values of 156.1±48.4 Hz to 146.8±48.1 Hz in producing neutral and 201.7±66.6 Hz to 186.5±64.7 Hz in happy prosody after the left-sided stimulation. Increased F0modulation from 201.7±66.6 Hz to 206.±78.7 Hz was found only in happy prosody after the right-sided stimulation. No significant changes were observed after sham stimulation. Conclusion: The DLPFC and its connections to the anterior cingulate cortex (ACC) play important role in production of emotional prosody. The left part of DLPFC refers to more motor components of emotional speech like initiation of mean F0. The right part is assumed to refine articulation by more emotional intonation realized through modulation of F0.