Limbic Encephalitis With Dual Positivity.

Limbic encephalitis is a well-defined clinical disorder among paraneoplastic neurological syndromes. Although it is not always possible to identify specific autoantibodies in limbic encephalitis, the presence of anti-neuronal nuclear antibody type 1 (ANNA1 or anti-Hu), anti-Ma2, collapsin response mediator protein 5 (CRMP-5-IgG or anti-CV2), anti-GABAB receptors and anti-amphiphysin antibodies are often detected. A 66-year-old male patient with complaints of forgetfulness was evaluated in our clinic after having seizures. In the neurological examination, the patient was found to be confused. In cranial MR fluid-attenuated inversion recovery (FLAIR) and T2-weighted images, the right hippocampal and parahippocampal structures showed hyperintense areas complying with limbic encephalitis. He had improvement with a course of 2 g/kg intravenous immunoglobulin (IVIG) followed by high-dose methylprednisolone therapy. Following the high-dose methylprednisolone therapy, anti-PCA1 (Yo) and anti-amphiphysin antibodies were positive and the tissue pathology report confirmed combined small-cell carcinoma and large-cell neuroendocrine carcinoma of the lung. In recent years, paraneoplastic neurological syndromes are better recognized with the identification of specific antibodies and the ubiquitous information on pathogenesis. This is the first known report in the literature that a case with both positive anti-PCA1 (Yo) and anti-amphiphysin antibodies together and underlying small-cell and large-cell neuroendocrine carcinomas.

Severe neuro-Behcet's disease treated with a combination of immunosuppressives and a TNF-inhibitor.

Abstract/ Resumo Behcet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD), is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI) findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days) and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day), iv cylophosphamide (1g) and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day) and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in NBD. Although combination of TNF inhibitors and cyclophoshamide is a rare therapeutic approach, it may be life-saving. However a higher awareness is required for opportunistic infections.

A severe case of systemic lupus erythematosus with increased pressure communicating hydrocephalus.

Normal/increased pressure hydrocephaly is an unusual manifestation of systemic lupus erythematosus (SLE), and the pathogenesis is still unclear. We report the case of an 18-year-old white female with severe refractory renal and pulmonary involvement who developed stupor during intensive immunosuppressive treatment. Enlarged ventricles on imaging and increased intracranial pressure with the exclusion of infectious and hemorrhagic/thrombotic processes suggested increased pressure communicating hydrocephalus associated with SLE. Few case reports are reviewed, and potential pathophysiologic mechanisms are discussed.

Dysexecutive syndrome: a specific pattern of cognitive impairment in systemic sclerosis.

BACKGROUND AND PURPOSE: Systemic sclerosis (SSc) is a connective-tissue disorder characterized by microvascular damage and tissue fibrosis. Although overt nervous system involvement is unusual in SSc, imaging studies have shown cerebral hypoperfusion. We evaluated cognitive functions in patients with SSc who had no history of neurological involvement, to seek cognitive impairment caused by the suggested cerebral hypoperfusion. METHODS: We performed a comprehensive neuropsychological test battery on 31 patients with SSc and on 2 groups of age-adjusted, sex-adjusted, and education-adjusted controls: 15 patients with rheumatoid arthritis and 20 healthy volunteers. RESULTS: The patients with SSc scored significantly worse on most of the measures of executive function than the 2 control groups (P<0.05). However, both patient groups did worse than the healthy controls on measures of attention and memory (P<0.005). CONCLUSIONS: Our results suggest that patients with SSc have a specific pattern of cognitive impairment: the dysexecutive syndrome. Attentional and memory problems, however, may arise from other confounders such as disease duration and chronic medication use. SSc may be a rare cause of vascular cognitive impairment.

The effects of verbal reaction time in Alzheimer's disease.

OBJECTIVES/HYPOTHESIS: Verbal fluency deteriorates with normal aging, but is much more severe in Alzheimer's Disease (AD). Verbal functions were analyzed to find differences between normal aging subjects in patients with mild cognitive impairment (MCI), and in patients with early and moderate stages of AD. This study measured the verbal response time in patients with AD, MCI, and in control subjects STUDY DESIGN: This study measured the verbal response time in patients with AD, MCI, and in control subjects METHODS: Fifteen patients with MCI, 15 patients with early AD, 8 patients with moderate AD, and 15 subjects for controls were included in the study. Word length in milliseconds, reaction time to a phoneme, word, or sentence and acoustic analysis of voice quality and speech diadochokinetic rate (DDK) were measured. RESULTS: Reaction time for a phoneme, word, or sentence especially the initiation period for them were longer in patients with early AD compared to patients with MCI (P < .001). The mean DDK rate was lower with increased severity of the disease, and was much more severe in patients with moderate AD. CONCLUSIONS: Clinical discrimination of the early stages of AD and MCI is challenging. Unfortunately, there are no laboratory markers present for the diagnosis of preclinical cases of AD. With the results of this study, the assessments of verbal reaction time may helpful for diagnosis of early AD.

The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study.

Cognitive impairment can occur at all stages of Parkinson's disease. Rasagiline is a selective monoamine oxidase type-B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinson's disease. This was a randomized, double-blind, placebo-controlled prospective study. Patients with Parkinson's disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinson's disease dementia. Fifty-five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span-backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit-ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type-B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinson's disease with cognitive impairment.

Psychotic depression: a peculiar presentation for multiple sclerosis.

Multiple sclerosis (MS) is frequently associated with a number of different psychiatric syndromes. Solely psychiatric syndrome may be the first clinical presentation of multiple sclerosis. We report a patient whose first attack was psychotic depression. The present case emphasizes that psychiatric symptoms can occur at any time during the course of the disease and, moreover, may be the presenting feature.

Glycine transporter-1 expression in the rat model of cortical dysplasia.

OBJECTIVE: Glycine transporter-1 (GLYT1) is an early marker of neural development and involved in the excitatory transmission in cortex. The study was designed to investigate the expression of GLYT1 in different parts of the brain by immunohistochemistry in the rat cortical dysplasia model. METHODS: On postnatal day 0, one freeze lesion was carried out on ten rats between bregma and lambda on the skull in the right hemisphere for 5 seconds. Six weeks later, rats were transcardially perfused with fixative and then their brains were removed for both hamotoxylin-eosine (H&E) staining for histopathology and immunohistochemistry staining for glial fibrillary acidic protein (GFAP) for astrocytic activity and GLYT1 in the cortical dysplastic region and other rostral brain regions involving epileptogenesis such as hippocampus, pyriform cortex, amygdala, thalamus and substantia nigra. RESULTS: GFAP immunoreactivity showed clusters of glial cells in the area of the microgyrus. Dense GLYT1 expression was localized to superficial layer of microgyric cortex and around the microgyrus. GLYT1 immunoreactivity was not detected in the other rostral regions. DISCUSSION: GLYT1 stained superficial structures might correspond to immature neuron and higher concentrations of GLYT1 around microgyrus might be correlated with increased excitatory mechanisms in these regions.

Intracranial sewing needle in a man with seizure: a case of child abuse?

Physical abuse in infancy can cause persistent neurological deficits. Although intracranial foreign bodies are generally secondary to penetrating trauma or surgical procedures, rarely they also occur as a result of child abuse. A 32-year-old man presented with the complaint of generalized tonic clonic seizures to the Neurology Department of Marmara, University Hospital. Computerized tomography (CT) scan revealed a sewing needle located within the temporal lobe. The location and the position of the needle suggested that it must have been introduced in infancy through the lamdoid suture before the closure of it, as an unsuccessful deliberate homicide attempt or accidental injury.

Effects of decompressive surgery on prognosis and cognitive deficits in herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) is a serious viral infection with a high rate of mortality. The most commonly seen complications are behavioral changes, seizures and memory deficits. We report the case of a 37-year-old man with HSE in the right temporal lobe and a severe midline shift who was treated with acyclovir. The patient underwent anterior temporal lobe resection. Although HSE can cause permanent cognitive deficits, in this case, early surgical intervention minimized any deficit, as determined by detailed neuropsychological examination. Surgical decompression is indicated as early as possible in severe cases. This case report emphasizes the effect of surgical decompression for HSE on cognitive function, which has rarely been mentioned before.

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C.

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.

Evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of ischaemic stroke.

Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with increased incidence of stroke in some populations, although contradictory results have been reported. The aim of this study was to determine the allelic frequency and the genotypic distribution for ACE gene polymorphism in Turkish patients with ischemic stroke compared to appropriate healthy controls and to correlate the genetic findings with stoke type. One hundred and eight patients with ischemic stroke versus 79 healthy controls were studied for the presence of ACE gene polymorphism detected by PCR. Genotypes were defined as DD, II and ID according to the presence of the D (deletion) and I (insertion) alleles. There was no statistically significant difference in either the genotypic distribution or allelic frequency between the patients versus healthy controls (chi2 = 0.105; df = 1; p = 0.430). There was also no significant difference for ACE genotype distribution and allelic frequency within the stroke group classified according to Bamford criteria (chi2 = 4.827; df = 3; p = 0.185). Our data supports lack of association between DD genotype and/or D allele and ischemic stroke or subtypes of ischaemic stroke in the Turkish population.

Short-wavelength automated perimetry in patients with migraine.

BACKGROUND: The aim was to investigate short-wavelength sensitivity deficits in patients with migraine. METHODS: Fifteen migraine and 18 age-matched healthy volunteers with normal ophthalmologic examination participated in this study. Migraine characteristics were graded by the Migraine Disability Assessment Questionnaire (MIDAS). All participants underwent SWAP (short wavelength amplitude perimetry) testing using a Humphrey field analyzer; there was a 30-2 presentation pattern. RESULTS: Short wavelength amplitude perimetry parameters for mean deviation (MD; p<0.0001) and pattern standard deviation (PSD; p<0.0001) were significantly worse in the migraine group. In the migraine group 53.3%. of eyes had glaucoma hemi-field tests (GHT) outside normal limits and 10 of these had early glaucomatous visual field loss. Statistically significant correlations were found between frequency of migraine attacks and MD (p=0.02; r=0.56) and PSD (p=0.03; r=0.41) and also between the MIDAS score and MD (p=0.03; r=0.49) and PSD (p=0.04; r=0.51). In all migraine cases with early glaucomatous visual field defect a corresponding site of the head was predominantly involved in headache (p=0.03). CONCLUSION: Some patients with severe migraine have earlier defects on SWAP suggesting a common vascular insult of glaucoma and migraine, and all migraine cases with high MIDAS scores should be further evaluated for early glaucomatous visual field defects using SWAP.

VEGF protects brain against focal ischemia without increasing blood--brain permeability when administered intracerebroventricularly.

Delayed administration of vascular endothelial growth factor (VEGF) promotes functional recovery after focal cerebral ischemia. However, early intravenous injection of VEGF increases blood-brain barrier (BBB) leakage, hemorrhagic transformation and infarct volume whereas its application to cortical surface is neuroprotective. We have investigated whether or not early intracerebroventricular administration of VEGF could replicate the neuroprotective effect observed with topical application and the mechanism of action of this protection. Mice were subjected to 90 mins middle cerebral artery (MCA) occlusion and 24 h of reperfusion. Vascular endothelial growth factor (8 ng, intracerebroventricular) was administered 1 or 3 h after reperfusion. Compared with the vehicle-treated (intracerebroventricular) group, VEGF decreased the infarct volume along with BBB leakage in both treatment groups. Neurologic disability scores improved in parallel to the changes in infarct volume. Independently of the decrease in infarct size, VEGF also reduced the number of TUNEL-positive apoptotic neurons. Phospo-Akt levels were significantly higher in ischemic hemispheres of the VEGF-treated mice. Contrary to intracerebroventricular route, intravenous administration of VEGF (15 microg/kg) enhanced the infarct volume as previously reported for the rat. In conclusion, single intracerebroventricular injection of VEGF protects brain against ischemia without adversely affecting BBB permeability, and has a relatively long therapeutic time window. This early neuroprotective action, observed well before recovery-promoting actions such as angiogenesis, possibly involves activation of the PI-3-Akt pathway.

The clinical profile of nonmotor fluctuations in Parkinson's disease patients.

OBJECTIVE: Recently described nonmotor fluctuations may cause disability in Parkinson's disease patients. These fluctuations are generally grouped as sensory, autonomic and psychiatric. The clinical spectrum and frequency of these fluctuating symptoms are not well-described. METHODS: We studied the relationship of nonmotor fluctuations with motor symptoms and determined the influence of age at disease onset, duration of disease, dosage and duration of levodopa treatment in the appearance of nonmotor fluctuations. RESULTS: Statistical analysis showed a relationship of disease-related parameters with sensory and autonomic fluctuations but psychiatric fluctuations were only found to be associated with the duration of levodopa usage. The nonmotor fluctuations included in the study were observed during "on" periods as well as "off' periods. CONCLUSION: Nonmotor fluctuations had variable presentations. Moreover, their co-appearance with different types of motor fluctuations may be linked to the effect of other neurotransmitter systems acting synchronously with dopamine. Risk factors for sensory and autonomic fluctuations in patients with Parkinson's disease were early age of disease onset, longer duration and higher dose of levodopa use. Psychiatric fluctuations were only associated with higher doses of levodopa.