Neurological Disorders

Introduction: The role of traditional risk factors in the pathophysiology of stroke (IS) has been established and is well know. It has recently been shown that 10 risk factors are associated with 90% of the risk of stroke. Material and methods: A case-crossover study design was used for the purpose of study. 2-hour hazard period immediately before the onset of stroke was compared with the 2-hour control period at the same time on the day before the onset of stroke. Results: The study assessed the role of seven potential triggers for stroke. Forty four patients (73%) reported exposure to at least one potential triggering factor during the 2 hours hazard period before onset of stroke symptoms. Twenty nine patients (66%) reported exposure to at least one of three (Anger, sudden change in posture, negative emotions) potential triggers during the 2-hour hazard period. Discussion: The current study examined possible association between exposure to potential triggers during a defined hazard period and triggering of the acute onset of stroke. There have been previously reported observations on the potential effect of emotions as a trigger for MI. Conclusion: The period of study and the study sample may not be large enough for extrapolation but nevertheless does open up a new area for research in our setup.

Objective: Primary intracranial leiomyomas are rare tumors. These tumors are mostly described in immunocompromised patients and associated with Epstein-Barr virus (EBV). The following report is an intracranial leiomyoma that was resected twice from a young, immunocompetent male. Methods: This is a report of a patient who initially presented with tremor and headaches. He was ultimately found to have a large 6 cm×8 cm tumor that was removed. Nine years later, he was found to have a small recurrence that was removed. No adjuvant therapies have been given. Results: His follow-up totals well over 11 years and he remains on observation. Extensive review of this rare entity is provided. Conclusion: It is suggested that observation without any adjuvant therapy be the treatment of choice after resection of primary intracranial leiomyomas. These uncommon, benign tumors should be followed long-term given their slow-growing nature.

Glycine encephalopathy also known as ‘Nonketotic Hyperglycinemia (NKH)’ is an autosomal recessive disorder caused by a defect in the glycine cleavage enzyme complex (GCS). The classic neonatal form typically presents with generalised hypotonia, lethargy, seizures, apnoeas and usually death by one year of age. In this report, we describe an unusual presentation of an infantile onset glycine encephalopathy presenting at 8 weeks of age with symptoms suggestive of gastro-oesophageal reflux (GOR) episodes. A normal neonatal developmental course in the first few months of life is the exception in this phenotype and has been rarely described in the literature. To the best of our knowledge this is the first case of glycine encephalopathy reported with initial symptoms suggestive of GOR.

A 52-year-old female presented with headache and double vision for one and half month. On examination of eye a horizontal nystagmus was seen in leftward gaze. Magnetic resonance imaging (MRI) brain showed multiple small rim and nodular enhancing lesion with mild perilesional edema in cerebral and cerebellar hemisphere and pons. Patient’s ESR was 70, and mountoux test was 14 mm after 72 hours. On the basis of MRI and investigations, and endemicity of tuberculosis in India, diagnosed as a case of tuberculoma and treated with anti tubercular treatment. She had 3 months of follow-up period and showed a complete amelioration of symptoms.

Background: Brain vessels play a relevant role in the development of malignant primary tumors. Previous studies performed in preclinical models of brain tumors demonstrated the irregular morphology of vessels in glioblastoma, characterized by multiple abnormalities in shape, permeability and relationship with the contacting structures, such as the basement membrane; however no data about microvascular structural alterations in the brain of patients affected by brain tumors have been previously reported. Methods: We studied small vessels structural alterations, microvascular rarefaction and vascular collagen content in the peritumoral brain tissue of two groups of patients, respectively affected by glioblastoma and by meningioma, who underwent a surgical operation in order to remove the tumor. The two groups of patients were matched for clinical, laboratory variables and risk factors, with the exception of sex. Results: Media to lumen ratio was significantly higher in patients with meningioma compared to patients affected by glioblastoma. Vessels in the brain surrounding glioblastomas show a less organized structure, as demonstrated by the thinner media, by the lower content in collagen and by the lower capillary density. Conclusions: For the first time, we used an in vitro ex vivo technique to analyze structural alterations of resistance sized arteries of peritumoral brain tissue at the radiological tumor-brain interface in patients affected by glioblastoma and meningioma. This approach, together with immunohistochemical evaluation of microvessel density, has supplied new data about the brain microcirculation. These findings can be the result of the aberrant angiogenic process that characterizes glioblastomas and can finally play a role in tumor growth. Further studies are needed to confirm our data, to identify the pathways that lead to this microvascular pattern and to identify possible clinical applications

The scientific literature contains a multitude of papers linking homocysteine to poor health. Elevated homocysteine levels have been linked to cardiovascular disorders, an increased risk of fractures in the elderly and to neurological conditions. Parkinson’s Disease is the second most prevalent neurodegenerative disorder after Alzheimer’s disease. It is characterised primarily by the loss of dopaminergic neurons of the substantia nigra pars compacta leading to movement disorders. In vitro data has demonstrated a marked deleterious effect of homocysteine on the neurons that die in Parkinson’s. Yet population-based studies reveal mixed results as to whether or not elevated homocysteine is a risk factor for Parkinson’s development. Nonetheless it is well known that the use of levodopa to alleviate symptoms of Parkinson’s leads to hyperhomocysteinemia, and that patients with the highest levels of homocysteine deteriorate faster than those with lower homocysteine titres. Thus homocysteine is of clinical significance for Parkinson’s patients and a fuller understanding of its effects on neuronal biochemistry and function will lead to better strategies to maintain quality of life for Parkinson’s sufferers.

The present study was performed to investigate whether or not lamotrigine (an anti-epileptic drug by sodiumchannel blockade and also increases gamma-aminobutyric acid [GABA]) could increase some anti-oxidant markers in the nucleus accumbens of mice exposed to picrotoxin as a model simulating convulsions in human. The results indicated that the anti-epileptic drug significantly increased the activities of glutathione peroxidase and catalase enzymes in nucleus accumbens homogenates as well as the contents of superoxide dismutase enzyme in red blood cells (RBCs) lysates in this model of convulsion. In addition the tested drug significantly decreased the level of the lipid peroxidation expressed as thiobarbituric acid-reactive substance (TBARS) in nucleus accumbens homogenates. So, the present study showed that the tested antiepileptic drug could potentiate its anticonvulsant activity via a possible anti-oxidant activity.

Botulinum toxin has been shown to reduce muscle tone and improve motor function in children and adults with muscle spasticity. However, it is not clear whether the magnitude and/ or the duration of the beneficial effect of this treatment are increased by combining it with other spasticity treatments. Nonetheless, some guidelines on the management of spasticity recommend that botulinum toxin is not used unless it is combined with other spasticity treatment modalities, such as physiotherapy. In this article it is argued that the clinical evidence that supports such recommendations is at best weak and that the recommendations are probably too restrictive. It is further suggested that the use of botulinum toxin as a stand-alone treatment of spasticity is justifiable, especially when other therapies are not immediately available for use in combination with the toxin.

Aim: Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA). It enhances both noradrenergic and 5HT 1 serotonergic transmission. The present study investigated the changes in forced swimming test and the alteration of GABA contents by this antidepressant drug in nucleus accumbens, as a part of the limbic system, from albino rats exposed to chronic mild stress (CMS)-induced anhedonia.

Methods: Albino rats were divided into 3 groups; group (1) received vehicle without exposure to CMS, group (2) received vehicle with exposure to CMS, group (3) received mirtazapine 16 mg/kg/day intraperitoneal (ip) dissolved in DMSO for 3 weeks during exposure to CMS.

Results: Reversal of CMS-induced anhedonia after 3 weeks ip administration of 16 mg/kg/day mirtazapine was observed. It modifies the behavioral changes recorded by the forced swimming test (FST) as well as the content of GABA neurotransmitter in their isolated nucleus accumbens.

Conclusion: The present study proposes the presence of a possible GABAergic role of mirtazapine in nucleus accumbens in the treatment of depressive disorders.

Erasistratus was born c. 325 B.C. on the island of Ceos (Chios), and died c. 250 B.C. He is remembered for his discoveries especially in physiology which were based on human and animal dissections and experiments. These discoveries provided new insights and additions to the Hippocratic corpus and Aristotelian concepts. Erasistratus, probably with Herophilus, discovered four ventricles as well as the convolutions of the cerebrum. He appreciated the separate neural pathways for motor and sensory functions and believed that the psychic pneuma was transmitted through motor nerves to muscles which contracted. He devised a corpuscular theory for physiological mechanisms of particle behaviour.

Gliomas, being the most prevalent and aggressive malignancy of the central nervous system, are associated with poor prognosis and very low survival rates. Failure of malignant glioma cells to respond to conventional cancer therapies is attributed to their infiltrating and immunosuppressive phenotype along with increased molecular heterogeneity. Current evidence implicates aberrant JAK-STAT signaling and expression of STAT inhibitors in the molecular pathogenesis of gliomas. This review provides a critical account of recent evidence regarding JAK-STAT signaling components in gliomagenesis, highlighting the potential therapeutic benefits and perspectives of targeting this pathway.

Introduction: The aim of our study was to present the results of intraventricular injection of recombinant tissuetype plasminogen activator (rtPA) in patients suffering from intraventricular hemorrhage (IVH). Material and methods: Patients with spontaneous IVH were enrolled in the study during 2006-2010. A rigid external ventricular drainage (EVD) was implanted via left or right sided frontal burr holes. 3 mg rtPA was injected each day over the EVD for three consecutive days. Hemorrhage size was determined by daily CT scanning. Classification of IVH was done using the IVH scoring system. The clinical condition was classified using the Glasgow coma scale (GCS) and Glasgow outcome scale (GOS). Statistical analysis (Fisher’s exact and χ²-Test) was done for various parameters to analyze their impact on outcome. Results: Eighty patients were included to the study (45 male, 35 female). At time of admission 49 patients (56.3%) were in a poor (GCS ≤ 8), 14 (17.5%) in an intermediate (GCS 9-12) and 17 (21.3%) in a good condition (GCS ≥ 13). In the majority of all cases clot lysis could reach a reduction of over 66%. However, clot lysis alone did not lead to a statistically significant reduction of morbidity and mortality (p>0.05). Poor GCS grade and age >70 years were statistically significant for poor outcome. Conclusion: Intraventricular application of rt-PA as a minimal invasive treatment modality seems to be suitable for clearance of the blood clots from the ventricles. Despite our mainly good and successful volume reduction, clot lysis alone did not influence the outcome positively. Its usage should be considered in view of different predictive factors. Large Prospective and randomized trials are necessary to answer the open questions.

The idea of “executive function” has become a fundamental concept in contemporary neurosciences. However, some disagreement remains around the question of unity or diversity (non-unitary) of executive functions and different points of view have been proposed. In this paper it is suggested that two major types of executive dysfunction syndromes can be separated: (a) Metacognitive executive dysfunction syndrome associated with dorsolateral frontal damage; and (b) Motivational/emotional executive dysfunction syndrome associated with orbitofrontal and medial frontal pathology. The first one is characterized by disturbances in intellectual abilities (“intelligence”), whereas the second one relates to impairments in behavioral control (disinhibition, impulsivity, etc.). Contemporary neuroimaging studies support this proposal.

Background: Clinical assessments of muscle tone are subjective, often using the non-affected side for comparison. The MyotonPRO offers portable, non-invasive, objective measurement of mechanical properties of muscles.

Objective: This study aimed to investigate between-limb symmetry for mechanical properties of biceps brachii (BB) in older males and within-session intra-rater reliability of a novice user of the MyotonPRO device.

Methods: Twenty community-dwelling, right-handed males aged 65-85 years (mean 71.7; SD ± 4.9) were studied. Exclusion criteria: history of neurological and musculoskeletal conditions, medications affecting muscle tone, and body mass index >30 kg/m2. The device applied 10 mechanical impulses at one second intervals, producing damped oscillations, from which frequency (non-neural tone), stiffness and logarithmic decrement (elasticity) were measured. With the participant resting supine, two consecutive sets of 10 recordings were taken bilaterally from BB.

Results: Percentage mean differences between-sides for larger and smaller values were 12% (tone), 14% (stiffness) and 27% (elasticity), which were statistically significant (p<0.001). Within-session reliability was excellent for all three parameters (ICC 3,2: all 0.99). Bland and Altman plots confirmed good agreement, without bias.

Conclusion: Symmetry of BB mechanical properties in a group of older males was less than 15% for tone and stiffness but not elasticity. Within-session intra-rater reliability of a novice user was excellent for all three parameters. Reliability over different days needs to be investigated. These findings indicate potential clinical application of the MyotonPRO for assessing abnormalities of muscle parameters in patients with neurological or musculoskeletal conditions, using comparison with the contralateral side (absolute difference), as well as databases of normative reference values from healthy control groups of different ages, gender and activity levels.

Our lab showed previously that whereas a substantial portion of chronically resected facial motor neurons reside in an atrophied state that can be reversed at 14 days following reinjury in wild-type (WT) mice, atrophy reversal was altered in immunodeficient mice. It was unclear, however, if the abnormal response at day 14 post-reinjury in immunodeficient mice might be due to differences in the kinetics of the reversal response or impaired regeneration. We sought to address this question, and test our working hypothesis that the normal regeneration of atrophied motor neurons is dependent on normal adaptive immunity, by comparing WT and immunodeficient recombination activating gene-2 knockout (RAG2- KO) mice that lack a mature T and B lymphocytes, at 3 and 28 days following reinjury. In WT mice, facial motor neurons that were resected for 10 weeks and subsequently reinjured for 3 days were able to regain fully an apparent 40% loss of countable neurons), and nearly 45% of that robust increase in neurons was sustained at 28 days post-reinjury in the WT mice. By contrast, at both 3 and 28 days post-reinjury RAG2-KO mice failed to show any increase in neuronal number. Size measurements showed that the surviving neurons of WT and RAG2-KO mice exhibited substantial motor neuron hypertrophy at 3 days post-reinjury, and similar levels of normal size motor neurons by 28 days post-reinjury. Among the WT mice, small numbers of T lymphocytes where found in the re-injured facial motor nucleus (FMN), and were significantly higher at 3 days, but not 28 days, in the reinjury compared to sham-reinjury groups. No differences were seen between the WT and RAG2-KO mice in overall microglial cell activity using CD11b expression following reinjury. These data suggest that many resected motor neurons did not survive the initial resection in RAG2-KO mice, whereas in WT mice they atrophied and could be restimulated by reinjury to regenerate their phenotype. Moreover, they indicate that normal T cell function, or some yet unknown function of the RAG2 gene in the brain, is essential for activating regeneration programs of atrophied motor neurons - programs with therapeutic potential for modifying neuroplasticity.