Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): A challenging diagnosis and a rare multiple sclerosis mimic.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an extremely rare hereditary cerebral small vessel disease caused by homozygous or compound heterozygous mutations in the gene coding for high-temperature requirement A serine peptidase 1 (HtrA1). Given the rare nature of the disease, delays in diagnosis and misdiagnosis are not uncommon. In this article, we reported the first case of CARASIL from Saudi Arabia with a novel homozygous variant c.1156C>T in exon 7 of the HTRA1 gene. The patient was initially misdiagnosed with primary progressive multiple sclerosis and treated with rituximab. CARASIL should be considered in the differential diagnosis of patients with suspected atypical progressive multiple sclerosis who have additional signs such as premature scalp alopecia and low back pain with diffuse white matter lesions in brain MRI. Genetic testing is important to confirm the diagnosis.

A novel mutation in ATM gene in a Saudi female with ataxia telangiectasia.

Ataxia telangiectasia is a hereditary multisystem disorder with a wide range of symptoms and signs. It is inherited in an autosomal recessive manner due to a mutation in the ataxia telangiectasia mutated (ATM) gene, which encodes a protein kinase with a domain related to a phosphatidylinositol 3-kinase (PI-3 kinase) proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. The characteristics of the disease include progressive cerebellar ataxia beginning between ages one and four years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctiva, immunodeficiency with frequent infections, and an increased risk for malignancy. In this article, we report a novel homozygous missense variant c.1516G > T, p.(Gly506Cys) in the ATM gene causing ataxia telangiectasia in a Saudi female. This variant led to the development of a later onset disease (at the age of 14 years) and the classical neurodegenerative process both clinically and on imaging. However, no immune system dysfunction or endocrine abnormalities were present. This is the second novel mutation in this gene so far reported from Saudi Arabia. The novel mutation described in the present study widened the genetic spectrum of ATM-associated diseases, which will benefit studies addressing this disease in the future.

Effectiveness and Needs Assessment of Faculty Development Programme for Medical Education: Experience from Saudi Arabia.

OBJECTIVES: Faculty members are the most important resource in any institution of higher education as medical education has been, and continues to be, a priority for medical colleges in Saudi Arabia. This study aimed to assess faculty members' perceptions of faculty development programmes (FDPs) in supporting important goals in medical education. In addition, this study aimed to assess faculty members' perceived needs. METHODS: This cross-sectional study was conducted between August 2016 and August 2017 and involved participants from six universities in Saudi Arabia's Western Province. The survey consisted of 31 items designed to assess FDP effectiveness and 49 items designed to assess needs in FDPs. RESULTS: A total of 210 faculty members participated in the study (response rate = 52.5%) and identified 49 needs. Faculty members perceived personal improvement in delivering medical education and the provision of greater educational involvement as the most effective considerations in an FDP. The respondents considered 13 needs to be of utmost importance; the remaining were considered important. CONCLUSION: This study assessed and identified faculty needs and important skills to consider when establishing an FDP. Furthermore, it provided information addressing the needs of, or gaps between, current and desired conditions in medical education in Saudi Arabia. The study also identified the most important elements (i.e. personal improvement) of faculty-perceived effectiveness for a successful FDP in medical education.

Idiopathic inferior rectus myositis: A rare cause of diplopia and a therapeutic success.

Orbital myositis is a rare inflammatory condition of a single or multiple extraocular muscles. It usually presents with unilateral or sequential bilateral sub-acute eye swelling, orbital pain, restricted eye movement, and redness of the eyelid. The swelling of extraocular muscles may lead to limited range of motion that produces blurred vision or diplopia. In this article, we report a male patient with idiopathic inferior rectus myositis presenting with diplopia who was managed successfully by medical and surgical intervention. Acute onset of diplopia with eye pain or limited extraocular movement is an ophthalmic emergency requiring urgent assessment and diagnostic imaging studies such as CT or MRI. The present case shows the crucial role of surgery as an adjunctive modality to achieve an improved clinical picture in patients not responding to immunosuppressive therapy. The secret to the success of management includes regular follow-up with frequent examination and comprehensive radiological and tissue investigations.

Hashimoto`s Encephalopathy Presenting with Progressive Cerebellar Ataxia.

Hashimoto`s encephalopathy is a rare neurological syndrome occurring in patients with autoimmune thyroid disease. The diagnosis of Hashimoto`s encephalopathy is based on the clinical picture with the presence of serum anti-thyroid antibodies regardless of the thyroid disorder. Acquired cerebellar ataxia associated with Hashimoto`s disease is a rare occurrence. In this article, we present a case who had progressive non-familial autoimmune pancerebellar disease in association with an increased level of thyroid peroxidase and thyroglobulin antibodies. The patient was managed aggressively with both intravenous immunoglobulins and plasma exchange, which stopped the progression of the disease and allowed for slow improvement. Early diagnosis of Hashimoto`s encephalopathy with autoimmune cerebellar ataxia and intervention with immunomodulatory therapy are of paramount importance. Close monitoring after steroid therapy is important since some patients with this rare disease might be resistant to steroid therapy and require aggressive immunomodulatory therapy.

Epilepsy and driving: Local experience from Saudi Arabia.

INTRODUCTION: The issue of epilepsy and driving has legal, social, and psychological implications. Many countries in the world restrict driving to people prone to epilepsy. There is no data from Saudi Arabia regarding the prevalence of driving among patients with epilepsy and their driving practices. In addition, to the best of our knowledge, there are no local laws or guidelines concerning driving for patients with epilepsy in Saudi Arabia. This study aimed to determine the prevalence of driving among male patients with epilepsy at King Abdulaziz Medical City in Jeddah, Saudi Arabia and determine the barriers and difficulties that they are suffering from especially when it comes to driving. METHODS: This is a cross-sectional study that was conducted between July 2017 and June 2018 at King Abdulaziz Medical City in Jeddah, Saudi Arabia. The inclusion criteria of this study were male patients with epilepsy 18 years of age or above. The exclusion criteria were female patients at any age (since they were not allowed to drive at the time of the study) and male patients less than 18 years of age. This study utilized a self-made self-administered 25-item questionnaire. RESULTS: A total of 182 surveys were distributed, and 164 individuals completed the survey (90.1% response rate). Most of the participants have a driving license (95.7%) and drive a car (98.8%). Almost all participants (99.4%) mentioned that nobody asked them whether they have epilepsy or not when issuing a driver's license. In addition, 94.5% were never told not to drive after the diagnosis of epilepsy. Regarding restrictions to driving, 98.7% reported that they drive at all times without any restrictions, and 92.7% reported that they drive both inside and outside the city. CONCLUSION: This study showed that the number of male patients with epilepsy driving cars was extremely high, accounting for almost all the patients in this study, with most of them doing several wrong practices during driving. Other major issues include the lack of specific laws regulating driving for patients with epilepsy and no counseling from physicians about driving after the diagnosis of epilepsy. We recommend developing the Saudi driving regulations for patients with epilepsy, and this study is considered an urgent call for action for the formation of a local driving regulations taskforce. Health education about the risk of driving should be disseminated, especially for patients with uncontrolled epilepsy.

A novel mutation in TTN gene in a Saudi patient with bilateral facial weakness and scapular winging.

Titin (TTN) is a large gene with 363 exons that encodes a large abundant protein (longest known polypeptide in nature) that is expressed in cardiac and skeletal muscles. TTN has an important role in the sarcomere organization, assembly of muscles, transmission of the force at the Z-line, passive myocyte stiffness, and resting tension maintenance in the I-band region. Mutation in extreme C terminus of TTN, situated at the end of M-band of the TTN in chromosome 2q31, results in tibial muscular dystrophy (TMD), also called Udd Distal Myopathy, which is an autosomal dominant distal myopathy. In this article, we report a novel mutation in TTN gene in a Saudi patient with bilateral facial weakness and scapular winging. This report adds to the literature a heterozygous missense variant c.85652C>G, p.(Pro28551Arg) in TTN gene, which may be related to genes that cause the disease, but more case validation is needed. The novel mutation described in the present study widened the genetic spectrum of TTN-associated diseases, which may benefit studies addressing this disease in the future.

A novel mutation in CACNA1A gene in a Saudi female with episodic ataxia type 2 with no response to acetazolamide or 4-aminopyridine.

Episodic ataxia is a genetically heterogeneous neurological condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia. Episodic ataxia type 2, caused by calcium voltage-gated channel subunit alpha1 A (CACNA1A MIM: 601011) mutation, is the most common form of episodic ataxia. It is characterized by recurrent attacks of imbalance associated with interictal nystagmus lasting hours to days and triggered by emotional stress or exercise. In this article, we report a novel heterozygous intronic variant c.5743+14A>G in the CACNA1A gene in a Saudi family. To the best of our knowledge, this variant has not been described in the literature or reported in public mutation databases. This report indicated that acetazolamide is not beneficial, and it may be even harmful to patients with episodic ataxia type 2 if used in later stages. In addition, treatment with 4-aminopyridine did not show any efficacy to improve walking or balance in our patient, which indicates the importance of early initiation of therapy before the later stages of the disease. Further research is needed to explore potential treatments for this challenging disease.

Ataxia with ocular apraxia type 2 not responding to 4-aminopyridine: A rare mutation in the SETX gene in a Saudi patient.

Ataxia with ocular apraxia type 2 is an autosomal recessive disorder caused by a mutation in the senataxin (SETX) gene. The disease is characterized by early onset cerebellar ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and increased levels of α-fetoprotein. Reported here is a rare homozygous frameshift deletion c.5308_5311del, p.(Glu1770Ilefs*15) in the SETX gene in a Saudi family. Ataxia with ocular apraxia type 2 was diagnosed based on the patient's history, an examination, and genetic testing. Genetic testing remains the only definitive method with which to identify the gene responsible. This is the third case report of this rare mutation in the literature. Ataxia with ocular apraxia type 2 continues to be a challenging disease to manage with no therapeutic options available to date. In the current case, the medication 4-aminopyridine was inefficacious in improving walking or balance. Further research is needed to identify potential treatments for this challenging condition.

Lacosamide-induced excessive laughing in a patient with Lennox-Gastaut syndrome.

Lacosamide is one of the third-generation antiseizure drugs that block voltage-gated sodium channels by enhancing slow inactivation. The most common adverse effects of lacosamide include dizziness, headache, nausea, vomiting, diplopia, fatigue, and sedation. Less common side effects include memory impairment, weight gain, rash, and atrioventricular block. In this article, we describe a patient with Lennox-Gastaut syndrome who developed excessive laughing as a rare side effect of lacosamide with complete resolution after discontinuation of the medication. The present case illustrates that excessive laughing may occur as an adverse effect of lacosamide.

Occupational Neurobrucellosis Mimicking a Brain Tumor: A Case Report and Review of the Literature.

Brucellosis is a zoonotic bacterial infection which is transmitted to humans from infected animals and is endemic in many parts of the world including Saudi Arabia. In this article, we report a case of occupational neurobrucellosis that presented with a space-occupying lesion mimicking a brain tumor. We stress on the importance of obtaining detailed social history including occupation to reach the diagnosis in several conditions including brucellosis. We also stress on taking universal precautions when handling any specimens. It may be advisable that manipulation of all unknown specimens arriving at the laboratory should occur in biological safety cabinet until a highly infectious organism is ruled out. Neurobrucellosis should be included in the differential diagnosis in patients presenting with solitary mass lesion mimicking brain tumor especially in endemic areas or high occupational risk group.

Idiopathic Harlequin Syndrome Manifesting during Exercise: A Case Report and Review of the Literature.

Harlequin syndrome is a rare autonomic disorder characterized by unilateral facial flushing and sweating with contralateral anhidrosis induced by exercise, heat, and emotion. It is usually idiopathic but could be the first manifestation of several serious underlying medical conditions. Medical or surgical treatments are not required for idiopathic Harlequin syndrome, but social and psychological factors may indicate sympathectomy or botulinum toxin injection. In this article, we report a case of idiopathic Harlequin syndrome and review the literature.

Vogt Koyanagi Harada Syndrome mimicking multiple sclerosis: A case report and review of the literature.

Vogt Koyanagi Harada (VKH) Syndrome, also called uveomeningioencephalitis, is a chronic disorder characterized by inflammation of the uvea, meninges, auditory system, and integumentary system. The association between VKH syndrome and multiple sclerosis (MS) has been reported only once in the literature in a patient who developed VKH syndrome after two years of the diagnosis of MS. In this article, we report a case who was misdiagnosed and treated as MS until she was proven to have VKH syndrome, and a diagnosis of MS was excluded. VKH syndrome is a systemic disorder that may present with clinical and/or radiological features mimicking MS. Applying diagnostic criteria is extremely important for confirming or excluding the diagnosis. Detailed history and physical examination are of paramount importance to score the final diagnosis. Rigorous search for red flags for both conditions is very helpful.

Biotin-thiamine-responsive basal ganglia disease: catastrophic consequences of delay in diagnosis and treatment.

BACKGROUND: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder caused by mutations in the SLC19A3 gene. The disease is characterized by subacute encephalopathy with confusion, dysphagia, dysarthria, and seizures. METHODS: We diagnosed a family affected by BTBGD and studied them including prognosis of cases when diagnosed and treated early in the disease process. We also review the literature comprehensively and summarize all published data about this disorder. RESULTS: Since its first description, a total of 89 cases (46 females and 43 males) have been published in the literature. We studied six patients in this article in which three died before a diagnosis was established, one was diagnosed lately and is currently severely affected, and two were diagnosed early and are currently stable on treatment. The clinical phenotype of each family member was studied in details. In addition, a genetic testing was performed using whole exome sequencing and Sanger sequencing which demonstrated a previously reported homozygous mutation in exon 5 of the SLC19A3 gene c.1264A>G (p.Thr422Ala). CONCLUSION: BTBGD is a treatable condition if recognized early and managed appropriately. The recognition of this disorder is important to avoid incorrect diagnosis and mismanagement. Children presenting with unexplained encephalopathy and MRI abnormalities including bilateral signal alteration of caudate nucleus and putamen should raise the suspicion for BTBGD and be started immediately on biotin and thiamine regimen since the prognosis of the disease is affected by the timing of treatment initiation. We present a large family affected with this disorder with severe interfamilial variability and different prognosis despite having the same mutation and same environment. A clear genotype-phenotype correlation and the clinical heterogeneity remain to be elucidated. Bad prognostic factors observed in our review include early onset of the disease, missed or delayed diagnosis, systemic involvements including respiratory failure and rhabdomyolysis, and severe neurological deficit or radiological changes at the time of diagnosis and treatment initiation. We observed during our literature review that all patients who presented since birth died despite aggressive treatment. This observation may illustrate that early presentation and disease process leads to a more catastrophic outcome.

Autosomal Recessive Cerebellar Ataxia type 1 mimicking multiple sclerosis: A report of two siblings with a novel mutation in SYNE1 gene in a Saudi family.

Autosomal Recessive Cerebellar Ataxia type 1 (ARCA1), also known as recessive ataxia of Beauce, is an adult onset pure cerebellar ataxia that typically presents with cerebellar ataxia and/or dysarthria. A mutation in the synaptic nuclear envelope protein 1 (SYNE1) gene that is located on chromosome 6p25 results in premature termination of the protein. It was first reported in 2007 as the first identified gene responsible for a recessively inherited pure cerebellar ataxia. In this article, we are presenting two brothers with ARCA1 who were misdiagnosed and treated as multiple sclerosis for more than a decade. We are not only presenting a rare mutation in a Saudi family, but we are also expanding on the heterogeneity of the clinical presentation of this disorder and elaborating on the pathophysiology of neurological involvement. These cases illustrate that white matter abnormalities on MRI may occur in ARCA1. The clinical and radiological spectrum of ARCA1 indicate that this disease is more than a pure cerebellar degeneration. ARCA1 should be considered in the differential diagnosis of patients diagnosed with MS especially in the presence of strong family history. The disease is gradually progressive, and clinical features are atypical for MS. Applying diagnostic criteria for MS is extremely important for confirming or excluding the diagnosis. Detailed history and physical examination are of paramount importance to score the final diagnosis. Another less likely possibility is a chance association, which may question the biological relevance of our data. To confirm or exclude this possibility, further studies reporting different cohorts need to be conducted.