Hashimoto encephalopathy--a difficult differential diagnosis. A case report of reversible dementia and psychosis

INTRODUCTION: Hashimoto encephalopathy is a rare disease that is associated with Hashimoto thyreoiditis. Dementia, disturbances of consciousness and epileptic seizures are the most common features. CASE REPORT: We report a case of Hashimoto encephalopathy in a 74-year-old woman who presented with psychotic episodes, visual hallucinations, dementia, tremor, rigidity and fluctuation of consciousness. After treatment with steroids, cognitive function became normal and other symptoms improved significantly. CONCLUSION: Hashimoto encephalopathy should be considered as a differential diagnosis of psychosis in combination with dementia and other neurological symptoms to dementia with Lewy bodies and Creutzfeldt-Jakob disease.     

Hashimoto encephalopathy

Hashimoto encephalopathy is a chronic relapsing steroid responsive encephalopathy characterized by antibodies against thyroid components. Etiology is still unknown. Confusion, seizures and coma are frequent reported symptoms. We present a 65-year old patient with acute onset of partial seizures and cognitive impairment. Hashimoto encephalopathy was assumed with diagnosis of Hashimoto thyroiditis and clinical syndrome. Symptoms resolved with thyroid treatment alone. Hashimoto encephalopathy should be considered in patients with unexplained encephalopathy, even when thyroid function seems to be normal.     

Seizures, psychosis and coma: severe course of hashimoto encephalopathy in a six-year-old girl

Hashimoto encephalopathy (HE) is a rare steroid-responsive encephalopathy associated with elevated antithyroid antibodies and is a well recognised complication of autoimmune thyroid disease. The clinical picture is pleomorphic, presenting with variable symptoms like coma, seizures, neuropsychiatric changes (impairment of cognitive functions, behavioural and mood disturbances, hallucinations) or focal neurological deficits. HE is mainly diagnosed in adults, but also a rare differential diagnosis of encephalopathy or epilepsy in children. The diagnosis is often overlooked at presentation but is crucial as it is a treatable disease. We report on the youngest patient described up to now presenting with progressive epilepsy resistant to anticonvulsive treatment and unclear encephalopathy related to Hashimoto thyroiditis.     

Mitochondrial Encephalopathy With Lactic Acidosis and Stroke-like Episodes (MELAS) May Respond to Adjunctive Ketogenic Diet

BackgroundMitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome can present management challenges. Refractory seizures and stroke-like episodes leading to disability are common.PatientWe analyzed the clinical, electrophysiologic, and radiologic data of a 22-year-old woman with multiple episodes of generalized and focal status epilepticus and migratory cortical stroke-like lesions who underwent muscle biopsy for mitochondrial genome sequencing.ResultsAlthough initial mitochondrial genetic testing was negative, muscle biopsy demonstrated a mitochondrial DNA disease-causing mutation (m.3260A > G). New antiepileptic medications were added with each episode of focal status epilepticus with only temporary improvement, until a modified ketogenic diet and magnesium were introduced, leading to seizure freedom despite development of a new stroke-like lesion, and subsequent decrease in frequency of stroke-like episodes. We propose a metabolic model in which the ketogenic diet may lead to improvement of the function of respiratory chain complexes.ConclusionsThe ketogenic diet may lead to improvement of mitochondrial dysfunction in MELAS, which in turn may promote better seizure control and less frequent stroke-like episodes.     

桥本脑病22例临床分析

目的 探讨桥本脑病临床特点,提高诊断与治疗水平.方法与结果 对22例桥本脑病患者的临床表现、实验室和影像学特点、治疗及预后进行回顾分析,临床主要表现为急性或亚急性发病的认知功能障碍（9例）、精神症状（6例）、癫（痫）发作（5例）、共济失调（5例）、卒中样发作（6例）、锥体外系症状（3例）和意识障碍（3例）,且血清抗甲状腺过氧化物酶抗体（19例）和抗甲状腺球蛋白抗体（20例）水平明显升高.其中21例经糖皮质激素冲击治疗,17例病情不同程度改善.结论 桥本脑病是一种伴抗甲状腺抗体水平升高的脑病,大多数患者对糖皮质激素冲击治疗反应良好,早期诊断、及时治疗对改善患者预后尤为重要.对于不明原因的脑病患者,应考虑桥本脑病的可能,推荐血清抗甲状腺抗体作为常规实验室检查项目.     

Differentiating early clinical features of Panayiotopoulos syndrome from acute encephalopathy

BackgroundPanayiotopoulos syndrome (PS) is a common benign epilepsy in childhood, characterized by predominantly autonomic symptoms such as emesis, pallor, and seizures, which are often prolonged. In an emergency room (ER), particularly when unconsciousness is prolonged, differentiating PS from acute encephalopathy is challenging. In this study, we aimed to elucidate the differences in clinical features of patients with PS and acute encephalopathy who visited our ER.MethodsWe retrospectively reviewed 18 patients who were transferred to our ER because of status epilepticus later diagnosed as PS, and 30 patients with acute encephalopathy, between July 2012 and July 2017. We compared patient demographics, clinical characteristics, and treatment.ResultsMost patients (90%) with acute encephalopathy had convulsive seizures of greater than or equal to 15 min, whereas only three patients (17%) with PS had convulsive seizures of greater than or equal to 15 min (P < 0.001). In addition, seizures were treatable in all patients with PS with a small dose of midazolam (0.1 mg/kg), but all patients with acute encephalopathy required midazolam at 0.3 mg/kg or more (P < 0.001). More patients with PS had autonomic symptoms compared to those with acute encephalopathy (e.g., vomiting [78% vs. 3%, P < 0.001]). Non-convulsive status epilepticus was observed in 22% of PS patients, but not in any acute encephalopathy patients. In contrast, fever was observed in all patients with acute encephalopathy (100%), but less frequently in those with PS (11%, P < 0.001).ConclusionPS was characterized by 1) convulsive seizures shorter than 15 min, 2) seizures treatable with small doses of midazolam, and 3) autonomic symptoms. PS could be differentiated from acute encephalopathy in the early stages of the syndrome.     

Hashimoto encephalopathy in pediatric patients: Homogeneity in clinical presentation and heterogeneity in antibody titers

Objective

Hashimoto encephalopathy is an autoimmune encephalopathy characterized by elevated antithyroid antibodies and a favorable response to corticosteroid. This study delineated the clinical characteristics of pediatric Hashimoto encephalopathy and the significance of low antithyroid antibody titers in diagnosis and treatment.

Recurrent status epilepticus as the main feature of Hashimoto's encephalopathy

Hashimoto's encephalopathy (HE) is a severe but treatable condition that rarely complicates Hashimoto's thyroiditis. Clinically it is characterized by progressive or relapsing symptoms, including tremor, myoclonus, stroke-like episodes, seizures, impairment of consciousness, and dementia. We describe a patient presenting with recurrent generalized convulsive status epilepticus (GCSE), despite antiepileptic medications, who was successfully treated with methylprednisolone. Our observation confirms that the clinical spectrum of HE at presentation is heterogeneous and diagnosis is often difficult. This case highlights the crucial importance of antithyroid antibody measurement in patients presenting with otherwise unexplained episodes of GCSE with or without adjunctive signs of encephalopathy or thyroiditis.     

Clonic seizures,continuous spikes-and-waves during slow sleep,choreoathetosis and response to sulthiame in a child with FRRS1L encephalopathy

BackgroundFerric chelate reductase 1 like (FRRS1L) encephalopathy is a rare cause of developmental and epileptic encephalopathy. Only a few cases have been reported thus far and seizures tend to be drug refractory. We report an additional case to highlight the good seizure response to sulthiame.Case reportA boy from non-consanguineous parents presented with history of ‘abnormal movements’ from 7 months of age. At one year of age, video electroencephalogram (EEG) monitoring demonstrated the ‘abnormal movements’ to be clonic seizures. Valproate, lamotrigine and clobazam combination were only partially effective at reducing the seizures. Repeat EEG at 1 year 8 months old revealed a continuous spikes-and-waves during slow sleep (CSWS) pattern, prompting a trial of sulthiame. After 2 weeks of sulthiame, seizures ceased completely. The clonic seizures recurred at age 4 years when sulthiame supply was interrupted, but the seizures promptly remitted following sulthiame’s resumption. Subtle choreiform movements appeared from age one year and later became more prominent. Whole exome sequencing (WES) identified a homozygous novel variant (nonsense) in the FRRS1L gene (NM_014334.3: c.670C>T:p.Gln224*). He has been seizure free since 4 years of age but remained profoundly delayed.ConclusionSulthiame may have a role in the early treatment of seizures in children with refractory epilepsy due to FRRS1L mutation.     

线粒体脑肌病伴高乳酸血症及卒中样发作的发病机制及临床研究进展

线粒体脯肌病伴高乳酸血症及脑卒中样发作（MELAS）是在1984年前首次被提出的,该病主要是由线粒体基因组第3243号位点的腺嘌呤突变为鸟嘌呤（m．3243A〉G）所导致。MELAS主要的神经系统表现为抽搐、脑卒中样发作和脑病,还包括一些其他症状如身材矮小、认知功能障碍、偏头痛、痴呆、心肌病、心脏传导阻滞和糖尿病等。本文主要从分子生物学角度讨论MELAS病的病因、诊断方式以及治疗手段的研究进展,着重阐述了细胞色素C氧化酶（COX）失调假说在MELAS病的发病机制中的作用。虽然MELAS病的治疗方法仍然有限,但是现有的和潜在的治疗方式值得探讨。     

Steroid-responsive encephalopathy in autoimmune thyroiditis: Clinical spectrum and MRI observations in three cases

Hashimoto''s encephalopathy (H.E.) is probably of autoimmune etiology, and manifests with seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, myoclonus. It is presumed to be autoimmune in origin with high serum titers of antithyroid peroxidase antibodies (anti-TPA). Thyroid function might often be normal. The diagnosis is arrived at by excluding other toxic, metabolic and infectious causes of encephalopathies, supportive clinical profile, elevated thyroid antibodies and optimum steroid response. We present the characteristic phenotypic manifestations, magnetic resonance imaging and electroechography observations and response to immunomodulation with follow-up in three cases of H.E. All the three cases manifested with subacute to chronic progressive encephalopathy, cerebellar dysfunction, seizures, behavioral abnormalities and oculomotor disturbances and had evidence of hypothyroidism, elevated titers of anti-TPA and positive thyroid anti-microsomal antibodies. Atypical and uncommon presentations are known. This report emphasizes that a high index of suspicion is often required in cases with “investigation negative encephalopathy” for early diagnosis of H.E.     

Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum

BackgroundPyridoxine-dependent epilepsy is a rare autosomal recessive epileptic encephalopathy caused by antiquitin (ALDH7A1) deficiency. In spite of adequate seizure control, 75% of patients suffer intellectual developmental disability. Antiquitin deficiency affects lysine catabolism resulting in accumulation of α-aminoadipic semialdehyde/pyrroline 6′ carboxylate and pipecolic acid. Beside neonatal refractory epileptic encephalopathy, numerous neurological manifestations and metabolic/biochemical findings have been reported.Methods and ResultsWe present a phenotypic spectrum of antiquitin deficiency based on a literature review (2006 to 2015) of reports (n = 49) describing the clinical presentation of confirmed patients (n > 200) and a further six patient vignettes. Possible presentations include perinatal asphyxia; neonatal withdrawal syndrome; sepsis; enterocolitis; hypoglycemia; neuroimaging abnormalities (corpus callosum and cerebellar abnormalities, hemorrhage, white matter lesions); biochemical abnormalities (lactic acidosis, electrolyte disturbances, neurotransmitter abnormalities); and seizure response to pyridoxine, pyridoxal-phosphate, and folinic acid dietary interventions.DiscussionThe phenotypic spectrum of pyridoxine-dependent epilepsy is wide, including a myriad of neurological and systemic symptoms. Its hallmark feature is refractory seizures during the first year of life. Given its amenability to treatment with lysine-lowering strategies in addition to pyridoxine supplementation for optimal seizure control and developmental outcomes, early diagnosis of pyridoxine-dependent epilepsy is essential. All infants presenting with unexplained seizures should be screened for antiquitin deficiency by determination of α-aminoadipic semialdehyde/pyrroline 6′ carboxylate (in urine, plasma or cerebrospinal fluid) and ALDH7A1 molecular analysis.     

Lithium-induced Hashimoto’s encephalopathy: a case report

Objective: To report on a patient with Hashimoto’s encephalopathy induced by lithium. Patient and interventions: A 61-year-old woman with a type II bipolar disorder and a history of lithium-induced thyrotoxicosis associated with silent thyroiditis was hospitalized to treat a severe major depressive episode. Given long-term treatment with levothyroxine for hypothyroidism that had resulted from silent thyroiditis, endogenous hormone in thyroid follicles was assumed to be minimized by the negative feedback, decreasing risk of recurrent thyrotoxicosis if lithium were restarted. Results: Lithium clearly relieved the patient’s depressive symptoms, but after 40 days encephalopathy developed. Thyrotoxicosis was ruled out, and serum antithyroid antibody titers were elevated. In the cerebrospinal fluid, protein content was substantially elevated and antithyroid antibodies were detected. Encephalopathy resolved dramatically after course of intravenous pulse therapy with methylprednisolone. Conclusions: We believe that autoantibodies against antigens shared by the thyroid gland and the brain were induced by exposure to lithium, causing the patient to develop Hashimoto’s encephalopathy.     

Epilepsy Characteristics and Clinical Outcome in Patients With Mitochondrial Encephalomyopathy,Lactic Acidosis,and Stroke-Like Episodes (MELAS)

BackgroundEpileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are heterogeneous with no pathognomonic features. We reviewed epilepsy characteristics and clinical outcome exclusively in a pediatric population.MethodsTwenty-two children and adolescents (13 males) with confirmed mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes due to mitochondrial DNA A3243G mutation and epilepsy were recruited. Clinical data including seizure semiology, treatment response, neuroimaging findings, and electroencephalography were analyzed. We also examined the effect of the age at seizure onset and initial symptoms on the clinical variables.ResultsSeizure semiology and electroencephalography abnormalities showed no syndrome-specific findings. Focal seizures occurred in 21 of 22 subjects (95.5%), whereas generalized seizures developed in seven of 22 subjects (31.8%). Twenty of 22 subjects (90.9%) achieved partial to complete reduction of clinical seizures for more than one year with a combination of more than two antiepileptic drugs. The subgroup with earlier seizure onset presented significantly earlier and showed significantly higher rates of drug-resistant epilepsy compared with the late onset group, although there were no significant differences in the initial symptoms. The subjects with severe epileptic conditions tended to have more severe clinical dysfunction and more severe organ involvement.ConclusionsBoth focal and generalized seizures occurred in patients with MELAS. Epilepsy in this population is drug resistant, but a certain degree of clinical seizure reduction was achievable with antiepileptic drugs, with more favorable outcomes than historically expected. Close observation and active epilepsy treatment of individuals with MELAS episodes and earlier seizure onset might improve the prognosis.     

Hashimoto’s encephalopathy mimicking Creutzfeldt-Jakob disease

Hashimoto’s encephalopathy is a rare, imprecisely defined autoimmune neurologic syndrome associated with Hashimoto’s thyroiditis that normally responds to corticosteroids. Here, we describe the case of a 55-year-old woman who presented with subacute cognitive decline and ataxia. Neoplastic, paraneoplastic, infectious, and metabolic etiologies were ruled out. Anti-TPO antibody level was markedly elevated at 966 U/mL. After one month of 60 mg/day of oral prednisone, she felt back to baseline and her Montreal Cognitive Assessment dramatically improved. Physicians should strongly consider this uncommon diagnosis in patients with rapid cognitive decline and no other clear etiology.     

Opsoclonus as a manifestation of Hashimoto’s encephalopathy

We present a 59-year-old male with early manifestation of opsoclonus associated with gait ataxia as a rare clinical presentation of Hashimoto’s encephalopathy. Empiric use of intravenous immunoglobulin followed by intravenous high dose methylprednisolone was initiated with subsequent remittance of opsoclonus, encephalopathy, ataxia, and tremor. Extensive workup for infectious, autoimmune, and paraneoplastic etiologies were undertaken and all studies were negative. Thyroglobulin antibodies (312 U/mL) and thyroid peroxidase antibodies (457 U/mL) were elevated (normal <60 U/mL) with a euthyroid state (thyroid stimulating hormone 3.13 μIU/mL). Three months after intravenous steroid therapy, the concentrations of thyroglobulin and thyroid peroxidase antibodies were retested and found to have decreased considerably. Thus, with steroid therapy, the patient’s opsoclonus and encephalopathy improved. We have presented a patient with a rare case of opsoclonus as the principal presenting feature of Hashimoto’s encephalopathy that was incompletely responsive to intravenous immunoglobulin and resolved with corticosteroids. This report underscores the importance for clinical practitioners to maintain a high index of suspicion for Hashimoto’s encephalopathy in cases of opsoclonus, especially when accompanied by an atypical presentation.     

Two types of early epileptic encephalopathy in a Pitt-Hopkins syndrome patient with a novel TCF4 mutation

IntroductionPitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by mutations in TCF4. Seizures have been found to vary among patients with PTHS. We report the case of a PTHS patient with a novel missense mutation in the gene TCF4, presenting with two types of early epileptic encephalopathy.Case reportThe patient was a Japanese boy. His first seizure was reported at 17 days of age, with twitching of the left eyelid and tonic-clonic seizures on either side of his body. An ictal electroencephalogram (EEG) showed epileptic discharges arising independently from both hemispheres, occasionally resembling migrating partial seizures of infancy (MPSI) that migrated from one side to the other. Brain magnetic resonance imaging revealed agenesis of the corpus callosum. His facial characteristics included a distinctive upper lip and thickened helices. His seizures were refractory, and psychomotor development was severely delayed. At the age of 10 months, he developed West syndrome with spasms and hypsarrhythmia. After being prescribed topiramate (TPM), his seizures and EEG abnormalities dramatically improved. Also, psychomotor development progressed. Whole-exome sequencing revealed a novel de novo missense mutation in exon 18 (NM_001083962.2:c.1718A > T, p.(Asn573Ile)), corresponding to the basic region of the basic helix-loop-helix domain, which may be a causative gene for epileptic encephalopathy.ConclusionsTo our knowledge, this is the first report of a patient with PTHS treated with TPM, who presented with both MPSI as well as West syndrome. This may help provide new insights regarding the phenotypes caused by mutations in TCF4.     

Persisting hyperekplexia after idiopathic, self-limiting brainstem encephalopathy.

Symptomatic hyperekplexia is a relatively rare entity, but has been documented in various, mostly brainstem diseases. We report the clinical and neurophysiologic vignette of a patient with a self-limiting, possibly inflammatory brainstem encephalopathy. Trismus was the presenting feature, but she later developed hyperekplexia. Although most brainstem features resolved spontaneously, the hyperekplexia has persisted.     

Pediatric Anti-NMDA (N-methyl D-Aspartate) Receptor Encephalitis

BackgroundWe report the clinical features and course of pediatric patients presenting with anti-N-methyl D-aspartate receptor (NMDA-R) encephalitis.MethodsSingle-center 4-year observational study of pediatric encephalitis associated with NMDA-R antibodies in the serum and/or the cerebrospinal fluid.ResultsThree girls with anti-NMDA-R encephalitis were identified. All presented with an acute hyperkinetic movement disorder and seizures, expressive aphasia, and emotional lability requiring inpatient treatment for 1-3 months. Imaging and electroencephalogram findings were nondiagnostic. None had an underlying tumor or ovarian teratoma. All received immune-modulatory therapy, including one or more of the following: high-dose methyl-prednisolone, plasma exchange, intravenous immunoglobulin or mycophenolate mofetil. Two of the three patients relapsed within 6 months of presentation and required retreatment with plasma exchange. All have remained in subsequent remission, with two of the three requiring second-line immunotherapy with rituximab.ConclusionsHyperkinetic movements in pediatric patients presenting with acute encephalopathy and prominent psychiatric symptoms should elicit a search for NMDA-R antibodies early in the evaluation. Relapses require aggressive immunomodulatory treatment for remission. This series highlights a unique positron emission tomography scan finding of hypermetabolism in one of the patients that correlated with her clinical symptoms. Recovery and rehabilitation can be prolonged, often taking years after the initial diagnosis. Early identification and treatment is likely to reduce relapses and limit morbidity associated with this potentially devastating but treatable encephalitis.     

Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-Like Episodes (MELAS): A Case Report and Critical Reappraisal of Treatment Options

ImportanceStroke-like episodes signal progression and significant disability in the mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes syndrome. Arginine is widely used as a treatment for stroke-like episode, although there is little evidence for this intervention. We discuss the management of a patient with mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes who presented with a stroke-like episode.ObservationDuring a seizure, which triggers the stroke-like episode, neurons are forced to utilize glycolysis as a source of adenosine triphosphate. Glycolytic by-products are damaging to the neuron. Breakdown of the blood-brain barrier leads to vasogenic edema.ConclusionTreatment of stroke-like episode should include anticonvulsants interictally to prevent seizures and dexamethasone ictally to help repair the blood-brain barrier.