Co-administration of probiotics and vitamin D reduced disease severity and complications in patients with Parkinson's disease: a randomized controlled clinical trial.

RATIONALE: Probiotics have beneficial effects on the nervous system by modulating the gut-brain axis. Additionally, vitamin D supplementation presents a potential way for ameliorating neuropsychological disorders, particularly in regions with a high prevalence of vitamin D deficiency. OBJECTIVES: The current clinical trial aimed to investigate the role of co-administered supplementation of probiotics and Vitamin D on the different inflammatory aspects of patients with Parkinson's disease. METHODS: Forty-six patients with PD were recruited From the Functional Neurosurgery Research Center, Tehran, Iran. These patients were randomly allocated to one of the two treatment groups: Group A, who received probiotic/vitamin D supplements (n = 23), and Group B who received placebo capsules (n = 23) for 12 weeks. As primary outcomes, Interferon-Gamma (IFN-γ), interleukin 1 beta (IL-1ß), IL-6, IL-10, Tumor Necrosis Factor-Alpha (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in serum were evaluated at the baseline and the end of the trial. Moreover, Additional questionnaire-based factors including gastrointestinal symptom rating scale (GSRS), Beck Anxiety Inventory (BAI), and Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. RESULTS: Our findings demonstrated that the consumption of probiotic/vitamin D supplements leads to a significant decrease in IL-1ß, INF-γ, IL-6, and MDA levels, while showing a significant increase in IL-10 and TAC levels compared to the placebo group (P < 0.05). Additionally, it leads to a significant decrease in the disease severity, anxiety, and gastrointestinal problems in PD patients in comparison to the placebo group (P < 0.05). CONCLUSIONS: Given the acknowledged role of inflammation in the pathogenesis of Parkinson's disease on one hand, and the recognized anti-inflammatory and antioxidant effects associated with probiotics and vitamin D on the other hand, the concurrent administration of probiotics and vitamin D supplements emerges as a promising and potentially effective treatment option for individuals with PD.

Patent foramen ovale leading to mismanagement in a mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes patient.

Key Clinical Message: The stroke-like episodes and brain MRI lesions in MELAS usually have a nonischemic pattern, are resolved over time, and have a migrating pattern that helps us distinguish them from ischemic cerebral infarcts. Nevertheless, conditions such as intracardiac thromboses, PFO, and hypercoagulable state may be present concomitantly, leading to mismanagement. Therefore, further investigation and echocardiography are suggested in MELAS patients. Abstract: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common maternally-inherited mitochondrial disorder presenting by stroke-like episodes, seizures, encephalopathy and muscle weakness. We report the clinical, imaging, echocardiography and muscle biopsy findings of a patient presenting by unique characteristics which have not been reported in previous cases of MELAS. The reported case is a 34 year old man with the history of three times hospitalization due to muscle weakness, encephalopathy, progressive cognitive decline, and gradual visual loss. Muscle biopsy revealed Ragged Red Fibers concomitant with mitochondrial disorders. PFO was found in echocardiography leading to mismanagement of this patient and MR imaging showed ischemic lesions with a progressive pattern. This is the first reported case of MELAS accompanying with PFO. All previous reported cases of MELAS have mentioned a fluctuating characteristic for the ischemic lesions; hence this is the first case of MELAS with the progressive pattern of ischemic lesions.

Third COVID-19 vaccine dose for people with multiple sclerosis who did not seroconvert following two doses of BBIBP-CorV (Sinopharm) inactivated vaccine: A pilot study on safety and immunogenicity.

Background: People with multiple sclerosis (pwMS) on anti-CD20 therapies (aCD20) and fingolimod have shown inadequate humoral responses to COVID-19 vaccines. Objective: The objective of the study was to pilot larger studies by demonstrating the safety and comparing the immunogenicity of different types of third doses in seronegative pwMS after two doses of BBIBP-CorV inactivated vaccine. Methods: In December 2021, subject to receiving their third dose, being COVID-19-naiive, and receiving no corticosteroid within two months, we measured the level of anti-SARS-CoV-2-Spike IgG in pwMS seronegative after two shots of BBIBP-CorV inactivated vaccine. Results: We included 20/29 pwMS who received adenoviral vector (AV), 7/29 who received inactivated, and 2/29 who received conjugated third doses. No serious adverse events were reported two weeks post-third dose. The pwMS receiving AV third doses showed significantly increased IgG concentrations, while only the ones not on aCD20 and fingolimod responded to inactivated third doses. An ordinal logistic multivariable generalized linear model indicated that age (per year ß: -0.10, P = 0.04), type of disease-modifying therapy (aCD20 ß: -8.36, P <0.01; fingolimod ß: -8.63, P = 0.01; others: reference), and type of third dose (AV or conjugated ß: 2.36, P = 0.02; inactivated: reference) are predictive of third dose immunogenicity among pwMS who remain seronegative after two shots of BBIBP-CorV vaccine. Statistical significance was not achieved for variables sex, MS duration, EDSS, duration of DMT, duration of third dose to IgG test, and duration from last aCD20 infusion to third dose. Conclusion: This preliminary pilot study highlights the need for further research to determine the optimal COVID-19 third dose vaccination strategy for pwMS living in areas where BBIBP-CorV vaccine has been used.

Longitudinal extensive transverse myelitis due to tuberculosis: A case report.

Neurotuberculosis is a potentially fatal disease that can present with upper or lower motor neuron symptoms. Longitudinally extensive transverse myelitis (LETM) is characterized by contiguous inflammatory lesions of the spinal cord extending to three or more vertebral segments. The causes of LETM include infections, neoplasm, and autoimmune diseases. Mycobacterium tuberculosis is a rare cause of transverse myelitis. Here, we report a 21-year-old Afghan female who was referred with chronic progressive quadriparesis and showed LETM on cervical MRI. This report indicates that tuberculosis should be considered as a differential diagnosis of LETM, especially in endemic areas.

Detection of anti-NMDA receptor antibodies following BBIBP-CorV COVID-19 vaccination in a rituximab-treated person with multiple sclerosis presenting with manifestations of an acute relapse.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a relatively unknown autoimmune entity. Scant reports of post-infection/vaccination anti-NMDAR encephalitis exist. We, hereby, reviewed the relevant cases and added to the literature a possible case of anti-NMDAR encephalitis following COVID-19 vaccination with BBIBP-CorV (Sinopharm). A 50-year-old Persian woman with previously known rituximab-treated MS presented complaining of worsening neurological symptoms all gradually starting and worsening after receiving the second dose of BBVIP-CorV 2 weeks before. Notable findings in her physical examination included ataxic gait and Babinski sign. Considering an acute MS relapse, corticosteroid pulse therapy was initiated, and she was referred for MRI, which revealed multiple new plaques. Her serum sample interestingly tested positive for anti-NMDAR antibodies. CSF analysis was unfortunately not performed. She responded well to the corticosteroid pulse therapy and showed substantial resolution of the symptoms. Considering its relatively low cost of workup and the benefits of correct early diagnosis, clinicians are advised to consider autoimmune encephalitis encountering patients with progressive neurological symptoms after the administration of vaccines, including the ones for COVID-19 which are currently being used extensively.

Focal epilepsy presenting as tongue tremor: A case report.

Plenty of etiologies are reported to cause tongue tremor. Focal epilepsy presenting as isolated tongue tremor is a rare condition, suggesting how variable the focal seizure presentation may be. This paper reports a case of focal epilepsy due to presence of a cavernous angioma in the region of cortical motor area related to tongue movements. It is an clinical example of pathological conditions affecting the tongue area in motor homunculus.

Centrally-located transverse myelitis would facilitate the differentiation of NMOSD and MOG-AD from MS.

OBJECTIVES: Differentiating neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) from multiple sclerosis (MS) is important since MS therapies might result in progression and relapse of the former diseases. Evidence of long extending transverse myelitis (LETM) in magnetic resonance imaging (MRI) is one of the requirements to make an NMOSD diagnosis. However, centrally located lesions on spinal MRI may bring higher sensitivity and specificity to the NMOSD and MOG-AD diagnosis. METHODS: We aimed to assess the association between NMOSD diagnosis and the presence of centrally located lesions at disease onset. We reviewed 102 medical records from the Isfahan MS clinic who presented with cervical cord lesions and 17 MS, 23 NMOSD, and 6 MOG-AD patients were selected. We collected demographic, clinical, and MRI data of patients who had clinical presentations of cervical cord lesion at disease onset, and the characteristics of the lesion were studied. RESULTS: There was an association between NMOSD diagnosis and presence of a centrally located lesion (CLTM) (P < 0.001), presence of an LETM (P < 0.001), and an intermediate to high axial cord expansion (P < 0.001). CLTM and LETM can also be found in MOG-AD patients. The presence of CLTM (sensitivity and specificity: 95.65% and 69.56%), possessed higher sensitivity and specificity for NMO diagnosis than LETM presence (sensitivity and specificity: 78.26% and 43.47%). CONCLUSION: A diagnostic criteria including the centrality, location, and expansion of the transverse myelitis lesions, in addition to LETM, may be more accurate in the diagnosis of NMOSD and MOG-AD and their distinction from MS.

Atherosclerosis and multiple sclerosis: An overview on the prevalence of risk factors.

BACKGROUND: Atherosclerosis is the leading cause of ischemic heart disease and coronary artery disease. The process of atherosclerosis develops over a period of years and is mainly immune-mediated. Data regarding the prevalence of vascular disease and atherosclerosis among people with multiple sclerosis (pwMS) is inconsistent, therefore, we aimed to provide an overview of the prevalence of atherosclerotic risk factors in pwMS. METHODS: This is a cross-sectional study over a period of one year among pwMS visiting the Isfahan MS center. Study data have been extracted using participants' files and a checklist that was completed by the observers. Only people with relapsing-remitting (RRMS) and secondary progressive (SPMS) forms of MS were included in the study. Participants with primary progressive (PPMS) disease are only described and have been excluded from analyses. RESULTS: Of the 396 pwMS (343 with RRMS and 53 with SPMS), in descending order, the reported risk factors were tobacco smoking (18.4%), dyslipidemia (10%), hypertension (8.8%), and diabetes mellitus (4.5%). In people with RRMS, 17.4% were smokers, 9.9% had dyslipidemia, 8.1% had hypertension, and 4.3% had diabetes mellitus. In SPMS patients 24.5% reported a history of smoking, 13.2% had hypertension, 9.4% had dyslipidemia, and 3.7% had diabetes mellitus. Smoking was insignificantly associated with higher expanded disability status scale (Z: 1.70, p-value = 0.090). Male sex (RR [95%CI]: 1.628 [1.172, 2.261], p-value = 0.004) and increasing age (RR [95%CI]: 1.024 [1.008, 1.040], p-value = 0.003) were associated with a higher number of risk factors. CONCLUSION: The highest observed atherosclerosis risk factor among pwMS was smoking. Diabetes mellitus was the least reported risk factor in our population as a whole. Overall, and in participants with RRMS, dyslipidemia and hypertension were the second and third most commonly reported risk factors, however, hypertension exceeded dyslipidemia in participants with SPMS. Male sex and increasing age were associated with a higher number of atherosclerosis risk factors.

Autoimmune encephalitis: the first observational study from Iran.

BACKGROUND: Even within the most populous countries in the Middle East, such as Iran, autoimmune encephalitis cases have been rarely reported. OBJECTIVE: We aimed to describe the demographic, clinical, and paraclinical characteristics of Iranian patients with autoimmune encephalitis positive for anti-neuronal autoantibodies. METHODS: This cross-sectional study included all patients diagnosed with autoimmune encephalitis and referred to our hospital, in Isfahan, Iran, from March 2016 to May 2020. Patients' demographic, clinical, laboratory, radiological, and electroencephalographic features were obtained from their medical records. RESULTS: We identified a total of 39 (21 females, 53.8%) patients with autoimmune encephalitis (mean age = 34.9 ± 12.8 years). The most commonly detected antibody was anti-NMDAR (n = 26, 66.7%), followed by anti-GABABR (n = 8, 20.5%), anti-Zic4 (n = 4, 10.3%), and anti-GAD65 (n = 1, 2.6%) antibodies, in descending order of frequency. Two anti-NMDAR-positive patients had a history of systemic lupus erythematosus (SLE), and four had a prior history of herpes simplex encephalitis. Clinical presentations in patients positive for anti-Zic4 antibodies included cognitive decline (n = 4, 100%), seizures (n = 3, 75%), parkinsonism (n = 1, 25%), and stiff-person syndrome (n = 1, 25%). CONCLUSION: This was the first case series of Iranian patients with autoimmune encephalitis with some interesting observations, including SLE-associated anti-NMDAR encephalitis, as well as an unusual concurrence of anti-Zic4 antibody positivity and cognitive problems, seizures, parkinsonism, and stiff-person syndrome.

Acute relapse and poor immunization following COVID-19 vaccination in a rituximab-treated multiple sclerosis patient.

With the progress of COVID-19 vaccination programs worldwide, some new adverse events associated with the available vaccines may unfold, especially in subpopulations, representatives of whom were not included in phase I, II, and III clinical trials of these vaccines, such as patients with autoimmune diseases, including multiple sclerosis (MS). A 34-year-old woman presented with severe right hemiplegia and ataxia. She was diagnosed with relapsing-remitting MS (RRMS) 13 years ago and treated with rituximab (an anti-CD20 monoclonal antibody) during the last 15 months. She had received her first dose of adenovirus-vectored COVID-19 vaccine Gam-COVID-Vac (Sputnik V) three months after her last infusion of rituximab and three days before experiencing her latest MS relapse episode, preceded by mild symptoms (fatigue, myalgia, generalized weakness, etc.). Magnetic resonance imaging revealed several new periventricular, juxtacortical, brainstem, and cerebellar peduncle lesions. She received corticosteroid therapy for five consecutive days, and her neurological deficits slightly improved. Twenty-one days after receiving the first dose of the vaccine, her anti-SARS-CoV-2 antibodies were below the lower detection limit. However, a decision was made to adhere to the vaccination schedule and not risk the patient's safety against an unfortunate COVID-19 contraction, and thus, she was advised to receive the second Gam-COVID-Vac dose after discontinuation of oral steroid taper. The safety of adenovirus-based vaccines in patients with autoimmune diseases requires further investigation. Meanwhile, clinicians should raise awareness among their patients regarding the potentially limited efficacy of COVID-19 vaccination in those treated with anti-CD20 treatments. After careful, individualized risk-benefit assessments, planning a delay/pause in such treatments to create a time window for patients to receive the vaccine and develop anti-SARS-CoV-2 immunity may be recommended.

Pneumocephalus as a rare complication: a systematic review plus clinical vignette.

INTRODUCTION: Pneumocephalus is a clinical entity characterised by the presence of gas in the intracranial space. It can result from many different causes. The most common cause is head or facial trauma. Other causes include neoplasms, infections, and surgical or diagnostic procedures. Spontaneous non-traumatic pneumocephalus is a rare condition caused by bone defects, malformations, infections, tumours, intravenous air injection, and other causes. This review, supplemented with a case presentation, aims to summarise the current state of knowledge regarding non-traumatic pneumocephalus. METHODOLOGY: This review involved an electronic search (PubMed, Scopus, Embase, and Web of Science) to identify studies regarding non-traumatic pneumocephalus. In addition, reference lists of identified articles were screened for other potentially relevant papers. RESULTS: In total, 1,107 articles were retrieved by searching databases with the selected query. Based on the selection process, 134 articles were included. These articles were then classified into 'otogenic', 'bone defect', 'malformations', 'infectious', 'tumours', 'associated with intravenous air injection', and other categories. CONCLUSION: Spontaneous non-traumatic pneumocephalus is a rare condition. Symptoms, clinical courses, and prognoses vary depending on the underlying cause of the disease. To the best of our knowledge, this review's example is the first case report of spontaneous pneumocephalus due to air embolism secondary to lung cancer.

"NMDA receptor spectrum disorder" in the differential diagnosis of demyelinating disorders of the CNS: optic neuritis and myelitis.

OBJECTIVE: The aim of this study was to investigate the frequency of anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody positivity in patients presenting with transverse myelitis (TM) and/or optic neuritis (ON), to describe their neurologic and radiological characteristics, and to compare these characteristics with those reported in previous studies. MATERIAL AND METHODS: This study included 179 patients (ON: 96, TM: 74, ON and TM: 9) who visited Isfahan Multiple Sclerosis Center from January 2017 to September 2019, for approximately 32 months. The respective neurological examinations were performed. Demographic data of the patients, as well as findings from radiological and serological investigations were obtained. RESULTS: Frequencies of anti-NMDAR seropositivity in patients with TM, ON, and concurrent TM and ON were approximately 3.4%, 1.4%, and 11.1%, respectively. None exhibited any psychiatric symptoms. CONCLUSION: Based on the frequency of seropositivity for anti-NMDAR antibody in our patients, positivity for this antibody appears to be more frequent than previously anticipated in patients presenting with these conditions. We recommend that the anti-NMDAR antibody presence in CSF/serum be checked and considered in addition to the routine examinations performed upon confronting demyelinating conditions such as TM and ON. We suggest considering the term "NMDAR spectrum disorder" to more clearly distinguish the potentially overlapping conditions with different etiologies in patients with CNS disorders.

Thalamic Ventral Intermediate Nucleus Deep Brain Stimulation for Orthostatic Tremor.

BACKGROUND: Orthostatic tremor (OT) was first described in 1977. It is characterized by rapid tremor of 13-18 Hz and can be recorded in the lower limbs and trunk muscles. OT remains difficult to treat, although some success has been reported with deep brain stimulation (DBS). CASE REPORT: We report a 68-year-old male with OT who did not improve significantly after bilateral thalamic stimulation. DISCUSSION: Although some patients were described who improved after DBS surgery, more information is needed about the effect of these treatment modalities on OT, ideally in the form of randomized trial data.

Gastrointestinal dysfunction in idiopathic Parkinsonism: A narrative review.

Currently, gastrointestinal (GI) dysfunctions in Parkinson's disease (PD) are well-recognized problems and are known to be the initial symptoms in the pathological process that eventually results in PD. Many types of PD-associated GI dysfunctions have been identified, including weight loss, nausea, hypersalivation, dysphagia, dyspepsia, abdominal pain, intestinal pseudo-obstruction, constipation, defecatory dysfunction, and small intestinal bacterial overgrowth. These symptoms can influence on other PD symptoms and are the second most significant predictor of the quality of life of these patients. Recognition of GI symptoms requires vigilance on the part of clinicians. Health-care providers should routinely ask direct questions about GI symptoms during office visits so that efforts can be directed at appropriate management of these distressing manifestations. Multiple system atrophy (MSA) and progressive supranuclear palsy are two forms of neurodegenerative Parkinsonism. Symptoms of autonomic dysfunctions such as GI dysfunction are common in patients with parkinsonian disorders. Despite recent progress in the recognition of GI dysfunctions, there are a few reviews on the management of GI dysfunction and GI symptoms in idiopathic Parkinsonism. In this review, the clinical presentation, pathophysiology, and treatment of each GI symptom in PD, MSA, and prostate-specific antigen will be discussed.

Convulsive syncope as presenting symptom of carotid body tumors: Case series.

Carotid body tumor (CBT) is paraganglioma and mainly found in the carotid bifurcation. The manifestations of the tumor are variable; in most cases, it presents as a non-symptomatic slow-growing mass, rarely compression of carotid body induces bradycardia and hypotension and repeated syncope, prolonged syncope can cause convulsion. Convulsive syncope occurred in 0.03% of patients with syncope. In this paper, we report three cases with CBT and convulsive syncope for which surgery was done and patients did not experience syncope again.