Schizophrenia (SCZ) is a debilitating mental illness that affects roughly 1% of the world's population. Current theories about the etiology of this disease highlight disruptions in dopamine (DA) and glutamine. However, a more recent theory, the 'synaptic hypothesis' proposes that the fundamental pathology of this illness involves disruptions in synaptic transmission. The synapsins are a family of neuron specific phosphoproteins that play an important role in neurotransmitter release, synapse formation and maintaining a reserve pool of synaptic vesicles. Previous research has suggested that synapsin II has a role in the etiology of SCZ. For example, synapsin II mRNA is significantly reduced in the medial prefrontal cortex (MPFC) of patients, and synapsin II knockout mice display a variety of behavioural abnormalities which mimic human SCZ. Considering that SCZ may result from changes in the synapse, we wanted to further elucidate the role of synapsin II by measuring protein expression in post-mortem PFC samples. Overall, our results revealed that synapsin IIa and IIb are not significantly different between patients and controls, however, we hypothesize that synapsin II expression has been normalized in patients due to antipsychotic drug (APD) use. In fact, we discovered that treatment with atypical APDs significantly increases synapsin II in the prefrontal cortex (PFC) of patients, which may underlie the beneficial effects of these drugs. Another objective of our work was to investigate the expression of various presynaptic proteins in post-mortem samples from patients with Parkinson's disease (PD) Parkinson's disease, like SCZ, is an illness which involves dysregulated dopaminergic transmission and synaptic dysfunction. Therefore, we hypothesized that synapsin II might also be disrupted in patients with PD. Our results demonstrated that synapsin IIa and IIb are significantly reduced in the substantia nigra (SN), but not the striatum (STR) or PFC of patients, when compared to controls. Further, no changes were observed in the other synapsins (I or III), or synaptophysin, which suggests that synapsin II dysregulation may be specific to disorders which involve disruptions in dopamine (DA). / Thesis / Master of Science (MS)

It is estimated that there are 12.5 million people in England living with neurological disorders (Neurological Alliance, 2014). People with neurological disorders as a result of acquired brain injury (ABI) are living with short and long-term disabilities. These include cognitive impairment, and physical and emotional distress. One of the most common complaints by individuals who have ABI is attention impairment. Attention difficulties can have serious ramifications for daily functioning. Although studies have explored the effects of evidence-based interventions such as mindfulness-based therapy on attention abilities, and have found that it improves individuals' attention skills (Moore et al, 2012), thus far research has been conducted mainly with non-clinical populations. This study set out to investigate whether a mindfulness-based intervention could prove beneficial for people with neurological disorders, particularly whether it could positively impact on attention impairment. The study employed a one group pre-test post-test design. The intervention was adapted from the MBSR programme developed by Kabat-Zinn. Twenty-two participants with ABI were recruited. The Conners Continuous Performance Test 3rd Edition (CPT-3), Mindful Attention Awareness Scale (MAAS), Attention Process Training-II Attention Questionnaire (APT-II AQ) and Clinical Outcome in Routine Evaluation-Outcome Measure (CORE-OM) were utilised to measure outcomes. The results revealed that there was a clinical improvement in self reported measures of mindfulness (MAAS) (Cohen d=0.28), attention (APT-II AQ) (Cohen d=0.33), and psychological distress (CORE-OM) (Cohen d=0.72). This was not observed using the neuropsychological test of attention (CPT-3) for overall group scores, but further evaluation showed some individuals' scores improved. The study is promising as it indicates that mindfulness based treatment can be effective with attentional problems as well as in reducing psychological distress for individuals with ABI. This could be valuable in terms of providing treatment for this client group and adds to the expanding research base on mindfulness-based intervention with this population.

Des mutations du gène ARX (aristaless-related homeobox gene) ont été identifiées dans un large spectre de désordres neurologiques précoces, incluant ou non des malformations cérébrales, le plus souvent associés à des épilepsies. Il est proposé que le gène ARX, codant pour un facteur de transcription, joue un rôle primordial au cours du développement cérébral, notamment sur la migration des neurones GABAergiques, mais son implication au cours de la mise en place du système nerveux central reste cependant encore mal connue. L’objectif de ce travail a été d’étudier le rôle du gène ARX et les conséquences de ses mutations sur le développement cérébral dans le but de mieux comprendre ces pathologies. Dans un premier temps, nous avons étudié l’effet d’une mutation particulière du gène, la mutation ARX(CGC)7, une expansion polyalanine retrouvée principalement dans des pathologies sans malformation cérébrale mais avec des épilepsies, tels que les syndromes de West ou d’Ohtahara. Des analyses réalisées sur une lignée de souris knock-in pour cette mutation (GCG)7 et sur des rats après électroporation in utero ont montré que la migration neuronale des neurones glutamatergiques et GABAergiques ainsi que la maturation des neurones GABAergiques ne sont pas altérées par cette mutation. De façon intéressante, nos données suggèrent que les épilepsies observées chez les souris knock-in résulteraient plutôt d’une réorganisation du réseau glutamatergique. Etant donné que le gène ARX n’est pas exprimé dans les neurones glutamatergiques, l’ensemble de ce travail suggère donc que les épilepsies chez les souris knock-in pour la mutation (GCG)7 sont la conséquence d’une altération développementale secondaire à la mutation initiale du gène, et ceci aurait d’importantes répercussions thérapeutiques qui requièrent d’avantages d’études. Des expériences nous ont ensuite permis d’étudier l’effet de plusieurs mutations du gène ARX sur la morphologie des interneurones in vitro. Celles-ci ont montré que les mutations d’ARX n’engendrent pas une localisation subcellulaire anormale de la protéine dans les interneurones en culture. De façon intéressante, ces expériences suggèrent que la morphologie des interneurones est altérée seulement par certaines mutations, notamment les mutations P353R et Dup24. Ces données soulignent ainsi l’importance d’étudier de façon spécifique chaque mutation du gène pour expliquer les mécanismes engendrant l’hétérogénéité phénotypique liée aux mutations d’ARX. L’ensemble de ces travaux contribuent à une meilleure compréhension du rôle du gène ARX dans le développement cortical et à une meilleure caractérisation des mécanismes physiopathologiques des désordres neurologiques précoces liés aux mutations de ce gène. / Several mutations in ARX gene (aristaless-related homeobox gene) have been found in a large spectrum of infantile neurological disorders, with or without cerebral malformation, but frequently linked to epilepsy. It has been proposed that ARX, coding for a transcription factor, plays a crucial role in brain development, especially in migrating interneurons, but its involvement in nervous system development still remains to be clarified. The aim of this work has been to study the role of ARX gene and the consequences of ARX mutations on cerebral development in order to better understand these pathologies.We have first investigated the effects of an ARX polyalanine expansion, the mutation (GCG)7, which was found in pathologies without brain malformation but associated to epilepsy, such as West and Ohtahara syndromes. Analysis performed on knock-in mice for this mutation and in utero electroporated rat brains have shown that this mutation doesn’t alter neither glutamatergic and GABAergic neuronal migration, nor GABAergic neuron maturation. Interestingly, our data suggest that epilepsy observed in knock-in mice would result rather from a reorganization of glutamatergic networks. Since ARX gene is not expressed in excitatory neurons, our work suggests that epilepsy observed in knock-in mice is the consequence of developmental alterations secondary to the initial mutation, and this would have crucial therapeutic implications that require additional investigations. In vitro experiments have then allowed us to study the effect of several ARX mutations on interneurons morphology. These experiments have shown no abnormal subcellular localization of ARX protein following transfection of these different mutations in cultured interneurons. Interestingly, our data show that interneuron morphology is altered only by some mutations, particularly the P353R and the Dup24 ARX mutations. Our data underline the importance to study specifically each mutation in order to explain mechanisms generating phenotypic heterogeneity linked to ARX mutations.Taken together, this study contributes to a better understanding of ARX involvement in cerebral development and to a better characterization of pathophysiological mechanisms linked to ARX mutations.

Introdução: A exposição ambiental ao chumbo é uma questão séria do ponto de vista de saúde pública, pois quando ocorre nos primeiros meses e anos de vida pode levar a sequelas neurológicas e comportamentais graves. Objetivos: 1- Determinar a concentração de chumbo obtida por meio de microbiópsias de esmalte realizadas in vivo em esmalte de dentes permanentes ou decíduos de pacientes com problemas neurológicos em tratamento ambulatorial no HCFMRP-USP e comparar os resultados em diferentes grupos de acordo com o diagnóstico. 2- Verificar o perfil dos valores de chumbo segundo informações relacionadas à exposição a esse metal dos referidos pacientes. Método: Uma microbiópsia foi realizada in vivo na superfície do esmalte de crianças de 5 a 12 anos, de ambos os gêneros, atendidas sequencialmente, sem conhecimento sobre a doença, em dois ambulatórios da área de Neurologia do HCFMRP-USP. O chumbo foi medido por espectrometria de absorção atômica com forno de grafite, e o fósforo foi medido colorimetricamente para determinarmos a profundidade da microbiópsia. Uma vez que a profundidade da microbiopsia não pode ser prevista, mas é um factor que influencia o resultado e que temos conhecimento que as concentrações de chumbo diminuem a partir da superfície para o interior do esmalte uma fórmula matemática foi utilizada para calcular a quantidade de chumbo que seria teoricamente encontrada em cada dente à mesma profundidade, e à profundidade seleccionada foi a média de todas as profundidades. As mães ou acompanhantes responderam a um questionário sobre fatores de risco de exposição ao chumbo. Os diagnósticos neurológicos foram obtidos por análise dos prontuários, posteriormente às microbiópsias, sendo criados cinco grupos independentes de crianças, com base na queixa principal: 1 - síndrome motora, SM (N=31); 2 - epilepsia, E (N=25); 3 - cefaléia, C (N=13); 4 - dificuldade escolar, DE (N=11); 5 - distúrbio do comportamento, DC (N=32). Resultados: A profundidade média das microbiópsias foi 3,16 m. Nas concentrações de chumbo obtidas não houve distribuição de Gauss, assim os valores de média, valores máximos e mínimos obtidos em cada grupo foram: 1 - 103,0, 395,0; 2,0. 2 - 64,8, 233,0; 4,0. 3 - 140,3, 434,0; 10,0. 4 - 135,8, 366,0; 38,0. 3 - 158,3, 476,0; 1,9. A análise dos valores de chumbo evidenciou que não houve correlação entre a idade das crianças e os valores de chumbo (Pearson r = -0,016; p = 0,86). Não se observou diferença significativa entre os gêneros (t-test p = 0,55) e também entre os dentes decíduos e permanentes (t-test p= 0,11). Quanto aos grupos com diagnósticos neurológicos, comparando os cinco grupos (ANOVA oneway), houve significância com valor de p= 0,004. O pós teste de Tukey evidenciou diferença significativa, sendo menores os valores de chumbo no grupo com epilepsia em relação aos grupos com dificuldade escolar e distúrbio de comportamento. Na análise dos fatores de risco, ocorreu maior número de crianças que brincam com pilhas no grupo cuja queixa principal era cefaléia em relação ao grupo com deficiência motora (p= 0,002). Não houve diferenças significativas, em nível de 5%, quanto aos valores de chumbo entre os casos com respostas positivas (p=0,53) ao questionário, nem entre as negativas (p=0,99) e nem entre ambos, comparando-se cada um dos fatores. O mesmo ocorreu na análise intragrupo para cada um dos cinco grupos de diagnósticos e entre os grupos. Conclusões: No presente estudo, encontramos maiores valores de chumbo no esmalte superficial em grupos de crianças com dificuldade escolar e distúrbio do comportamento em relação àquele com epilepsia; e ainda, o achado de que os fatores ambientais de risco estudados não tiveram relação com as diferenças observadas entre esses grupos suscita indagações e necessidade de aprofundamento em pesquisas sobre os efeitos danosos do chumbo no tecido neural, mesmo quando se trata de uma população que vive em áreas consideradas sem risco ambiental e com valores de chumbo no sangue (quando são medidos, o que não é o caso deste estudo) abaixo do limite de intervenção. / Background: The environmental exposure to lead is a serious issue from the standpoint of public health, because when it occurs in the first months and years of life it can lead to serious neurological and behavioral consequences. Objectives: 1 - To determine the concentration of lead obtained by an micro biopsy in vivo on permanent teeth enamel or deciduous teeth of patients with neurological problems in outpatient treatment in HCFMRP-USP and compare results in different groups according to diagnosis. 2 - To check the profile of the values of lead according to information related to exposure to the metal of these patients. Method: A micro biopsy was performed in vivo on enamel of children 5-12 years of both genders, attended sequentially, without knowledge of the disease in two clinics in the area of Neurology, USP-HCFMRP. Lead was measured by graphite-furnace atomic absorption spectrometry, and phosphorus was measured colorimetrically to determine the depth of the micro biopsy. Since the micro biopsy depth cannot be anticipated, but is a factor that does influence the result, since lead concentrations are known to decrease from the surface to the inner enamel, a mathematical formula was used to calculate how much lead would be theoretically found in each tooth at the same depth, and the depth selected was the mean of all depths obtained. The mothers or caretakers answered a questionnaire on risk factors for lead exposure. The neurological diagnoses were obtained by analyzing the charts, then the micro biopsy, and created five independent groups of children based on chief complaint: 1 - motor impairment, MI (N = 31), 2 - epilepsy, E (N = 25), 3 - headache, H (N = 13), 4 - school difficulties, SD (N = 11), 5 - behavioral disorder, BD (N = 32). Results: The mean micro biopsy depth of all tests was 3.16 m. The lead concentrations obtained did not follow Gaussian distribution, and median, maximal and minimum values for each group are as follows: 1 - 103,0, 395,0; 2,0. 2 - 64,8, 233,0; 4,0. 3 - 140,3, 434,0; 10,0. 4 - 135,8, 366,0; 38,0. 3 - 158,3, 476,0; 1,9. The analysis of lead values showed no correlation between the age of the children and the values of lead (Pearson r = -0.016, p = 0.86). There was no significant difference between genders (t-test p = 0.55) and also between the primary and permanent teeth (t-test p = 0.11). As for the groups with neurological disorders, comparing the five groups (one-way ANOVA) showed significant p-value = 0.004. The post Tukey test showed significant differences, with smaller values of lead in the group with epilepsy compared to those with school difficulties and behavior disorders. In the analysis of risk factors, a greater number of children playing with piles in the group whose main complaint was headache in the group with motor disabilities (p = 0.002). There were no significant differences in the 5% level, about the values of lead among the cases with positive responses (p = 0.53) to the questionnaire or between the negative (p = 0.99) nor between the two, comparing each of the factors. The same is true for the intragroup each of the five diagnostic groups and between groups. Conclusions: In the present study, we found higher values of lead in the enamel surface in groups of children with school difficulties and behavioral disturbances in relation to that with epilepsy, and also the finding that environmental risk factors studied were not associated with the differences observed between these groups raises questions and need for further research on the harmful effects of lead on neural tissue, even when the population leaves in an environment with no known contamination with lead and shows blood lead concentrations (which is not the case of this study) that are lower than the values considered harmful to health.

The common human GNB3 825C > T variant, which is present in 50% of the world’s chromosomes, has previously been shown to predispose individuals to hypertension, cardiac and neural disorders. This variant causes the production of a stable and gain of function protein Gβ_3S- This thesis describes the discovery of a novel D153del mutation that produces an unstable, loss of function, protein Gβ_3D in the recessively inherited, retinopathy globe enlarged (rge) chickens. This thesis also demonstrates that the normal Gβ₃ downstream phosphorylation signalling pathways are significantly altered in a tissue specific manner in rge chicken organs and in a human GNB3 825TT lymphoblast cell line. In rge tissues expressing Gβ_3D protein, the cAMP induced GRK2 phosphorylation activity is significantly altered. Moreover MAPK1 (ERK2) phosphorylation is significantly decreased compared to normal tissues. In contrast human 825TT cell lines expressing the Gβ_3S protein, showed enhanced cAMP induced GRK2 and MAPK (ERK1 and ERK2) phosphorylation activity. These results confirm previous findings of 825C > T Gβ₃ studies, that Gβ_3S is indeed a hyper-activating structural variant, in contrast to the D153del Gp3D is a classical recessively inherited non-functional mutation.

Introdução: A exposição ambiental ao chumbo é uma questão séria do ponto de vista de saúde pública, pois quando ocorre nos primeiros meses e anos de vida pode levar a sequelas neurológicas e comportamentais graves. Objetivos: 1- Determinar a concentração de chumbo obtida por meio de microbiópsias de esmalte realizadas in vivo em esmalte de dentes permanentes ou decíduos de pacientes com problemas neurológicos em tratamento ambulatorial no HCFMRP-USP e comparar os resultados em diferentes grupos de acordo com o diagnóstico. 2- Verificar o perfil dos valores de chumbo segundo informações relacionadas à exposição a esse metal dos referidos pacientes. Método: Uma microbiópsia foi realizada in vivo na superfície do esmalte de crianças de 5 a 12 anos, de ambos os gêneros, atendidas sequencialmente, sem conhecimento sobre a doença, em dois ambulatórios da área de Neurologia do HCFMRP-USP. O chumbo foi medido por espectrometria de absorção atômica com forno de grafite, e o fósforo foi medido colorimetricamente para determinarmos a profundidade da microbiópsia. Uma vez que a profundidade da microbiopsia não pode ser prevista, mas é um factor que influencia o resultado e que temos conhecimento que as concentrações de chumbo diminuem a partir da superfície para o interior do esmalte uma fórmula matemática foi utilizada para calcular a quantidade de chumbo que seria teoricamente encontrada em cada dente à mesma profundidade, e à profundidade seleccionada foi a média de todas as profundidades. As mães ou acompanhantes responderam a um questionário sobre fatores de risco de exposição ao chumbo. Os diagnósticos neurológicos foram obtidos por análise dos prontuários, posteriormente às microbiópsias, sendo criados cinco grupos independentes de crianças, com base na queixa principal: 1 - síndrome motora, SM (N=31); 2 - epilepsia, E (N=25); 3 - cefaléia, C (N=13); 4 - dificuldade escolar, DE (N=11); 5 - distúrbio do comportamento, DC (N=32). Resultados: A profundidade média das microbiópsias foi 3,16 m. Nas concentrações de chumbo obtidas não houve distribuição de Gauss, assim os valores de média, valores máximos e mínimos obtidos em cada grupo foram: 1 - 103,0, 395,0; 2,0. 2 - 64,8, 233,0; 4,0. 3 - 140,3, 434,0; 10,0. 4 - 135,8, 366,0; 38,0. 3 - 158,3, 476,0; 1,9. A análise dos valores de chumbo evidenciou que não houve correlação entre a idade das crianças e os valores de chumbo (Pearson r = -0,016; p = 0,86). Não se observou diferença significativa entre os gêneros (t-test p = 0,55) e também entre os dentes decíduos e permanentes (t-test p= 0,11). Quanto aos grupos com diagnósticos neurológicos, comparando os cinco grupos (ANOVA oneway), houve significância com valor de p= 0,004. O pós teste de Tukey evidenciou diferença significativa, sendo menores os valores de chumbo no grupo com epilepsia em relação aos grupos com dificuldade escolar e distúrbio de comportamento. Na análise dos fatores de risco, ocorreu maior número de crianças que brincam com pilhas no grupo cuja queixa principal era cefaléia em relação ao grupo com deficiência motora (p= 0,002). Não houve diferenças significativas, em nível de 5%, quanto aos valores de chumbo entre os casos com respostas positivas (p=0,53) ao questionário, nem entre as negativas (p=0,99) e nem entre ambos, comparando-se cada um dos fatores. O mesmo ocorreu na análise intragrupo para cada um dos cinco grupos de diagnósticos e entre os grupos. Conclusões: No presente estudo, encontramos maiores valores de chumbo no esmalte superficial em grupos de crianças com dificuldade escolar e distúrbio do comportamento em relação àquele com epilepsia; e ainda, o achado de que os fatores ambientais de risco estudados não tiveram relação com as diferenças observadas entre esses grupos suscita indagações e necessidade de aprofundamento em pesquisas sobre os efeitos danosos do chumbo no tecido neural, mesmo quando se trata de uma população que vive em áreas consideradas sem risco ambiental e com valores de chumbo no sangue (quando são medidos, o que não é o caso deste estudo) abaixo do limite de intervenção. / Background: The environmental exposure to lead is a serious issue from the standpoint of public health, because when it occurs in the first months and years of life it can lead to serious neurological and behavioral consequences. Objectives: 1 - To determine the concentration of lead obtained by an micro biopsy in vivo on permanent teeth enamel or deciduous teeth of patients with neurological problems in outpatient treatment in HCFMRP-USP and compare results in different groups according to diagnosis. 2 - To check the profile of the values of lead according to information related to exposure to the metal of these patients. Method: A micro biopsy was performed in vivo on enamel of children 5-12 years of both genders, attended sequentially, without knowledge of the disease in two clinics in the area of Neurology, USP-HCFMRP. Lead was measured by graphite-furnace atomic absorption spectrometry, and phosphorus was measured colorimetrically to determine the depth of the micro biopsy. Since the micro biopsy depth cannot be anticipated, but is a factor that does influence the result, since lead concentrations are known to decrease from the surface to the inner enamel, a mathematical formula was used to calculate how much lead would be theoretically found in each tooth at the same depth, and the depth selected was the mean of all depths obtained. The mothers or caretakers answered a questionnaire on risk factors for lead exposure. The neurological diagnoses were obtained by analyzing the charts, then the micro biopsy, and created five independent groups of children based on chief complaint: 1 - motor impairment, MI (N = 31), 2 - epilepsy, E (N = 25), 3 - headache, H (N = 13), 4 - school difficulties, SD (N = 11), 5 - behavioral disorder, BD (N = 32). Results: The mean micro biopsy depth of all tests was 3.16 m. The lead concentrations obtained did not follow Gaussian distribution, and median, maximal and minimum values for each group are as follows: 1 - 103,0, 395,0; 2,0. 2 - 64,8, 233,0; 4,0. 3 - 140,3, 434,0; 10,0. 4 - 135,8, 366,0; 38,0. 3 - 158,3, 476,0; 1,9. The analysis of lead values showed no correlation between the age of the children and the values of lead (Pearson r = -0.016, p = 0.86). There was no significant difference between genders (t-test p = 0.55) and also between the primary and permanent teeth (t-test p = 0.11). As for the groups with neurological disorders, comparing the five groups (one-way ANOVA) showed significant p-value = 0.004. The post Tukey test showed significant differences, with smaller values of lead in the group with epilepsy compared to those with school difficulties and behavior disorders. In the analysis of risk factors, a greater number of children playing with piles in the group whose main complaint was headache in the group with motor disabilities (p = 0.002). There were no significant differences in the 5% level, about the values of lead among the cases with positive responses (p = 0.53) to the questionnaire or between the negative (p = 0.99) nor between the two, comparing each of the factors. The same is true for the intragroup each of the five diagnostic groups and between groups. Conclusions: In the present study, we found higher values of lead in the enamel surface in groups of children with school difficulties and behavioral disturbances in relation to that with epilepsy, and also the finding that environmental risk factors studied were not associated with the differences observed between these groups raises questions and need for further research on the harmful effects of lead on neural tissue, even when the population leaves in an environment with no known contamination with lead and shows blood lead concentrations (which is not the case of this study) that are lower than the values considered harmful to health.

No description available.

Rasmussen’s encephalitis is a rare neurological disease first described in 1958 that is characterized by medico-refractory seizures, focal unilateral cerebral inflammation, and deficits such as hemiparesis. While we still do not have a full understanding of this disease, proposed theories behind its etiology include auto-immune manifestations, immune attack by T cells, and malfunctional alterations in genetic expression. It is classically considered a rare childhood malady with a median age of onset of six years, and cases in adolescents and adults are even rarer, representing up to 10% of all cases to date. In this report, we would like to share a rare case of Rasmussen's encephalitis that occurred in an adolescent. Our 17-year-old male patient presented with signs and symptoms beginning at age 14 and was initially diagnosed with cerebral palsy only to later present with additional symptoms and characteristic EEG and MRI findings that ultimately led to a diagnosis of Rasmussen’s encephalitis. Thus, with this case report, our intent is twofold: to shed light on an atypical presentation of an already rare disease, even rarer in adolescents and adults, and to underscore the importance of keeping a broad differential when it comes to evaluating a patient with seizures.

Introduction - Pure autonomic failure is a rare disorder characterized by orthostatic hypotension, absence of a compensatory rise in heart rate, and abnormal autonomic functions. In most cases, supine hypertension is seen coupled with orthostatic hypotension, making the management of these patients a big challenge. We present the case of a 74-year-old gentleman, who presented to the ED with altered mental status for a day; weakness, and falls for 3 weeks. The patient had a past medical history of Hypertension, alcoholism, and REM sleep disorder. He was being treated for erectile dysfunction for the last 10 years and had a family history of Parkinson's disease in his mother and sister. The patient was compliant with Lisinopril 40 mg, Amlodipine, and Rosuvastatin, Tamsulosin 0.4 mg. His blood pressure(BP) on presentation was ranging between 109/74-194/76 mm of Hg. Systolic BP dropped by 30mmHg after tilting the angle of the bed to 45 degrees for 1 minute with no change in HR and the patient became symptomatic in this position. Orthostatic vitals showed a dramatic drop in Systolic BP of >80mmHg with no change in heart rate. MRA and MRI showed chronic microvascular changes. The Echocardiogram, Cortisol, and TSH levels were all normal. All anti-hypertensives were discontinued and supportive treatment was started with Midodrine, Droxidopa, and Pyridostigmine, thigh-high TED hose and abdominal binders at bedtime, and Nitroglycerin patch at night for hypertension. The patient was started on fludrocortisone as he continued to drop his BP by 80 mmHg on standing. The use of TED stockings and bed tilting improved the issue of uncontrolled supine hypertension at night. Conclusion- Treatment of autonomic dysfunction continues to be challenging. There are no definitive guidelines and management is largely individualized. Both pharmacological and non-pharmacological measures are used.

No description available.