Amplitude-integrated electroencephalography in patients with acute encephalopathy with refractory, repetitive partial seizures

We report amplitude-integrated EEG findings in two children with acute encephalopathy with refractory, repetitive partial seizures. Both patients had a febrile illness one week before the onset of seizure. They had reduction of consciousness and repetitive seizures refractory to first-line antiepileptic drugs. Seizure frequency rapidly increased and evolved into status epilepticus. Continuous seizure monitoring with amplitude-integrated EEG revealed frequent subclinical seizures which were missed by direct observation. In addition, the site of origin of seizures was multifocal, and seizure foci shifted from one hemisphere to the other. Their seizures were controlled after an administration of high-dose phenobarbital. Continuous seizure monitoring with amplitude-integrated EEG will contribute to correct estimation of seizure burden and efficacy of antiepileptic drugs in children with acute encephalopathy with refractory, repetitive partial seizures.     

A Rasmussen encephalitis,autoimmune encephalitis,and mitochondrial disease mimicker: expanding the DNM1L‐associated intractable epilepsy and encephalopathy phenotype

Dynamin‐1‐like protein (DNM1L) gene variants have been linked to childhood refractory epilepsy, developmental delay, encephalopathy, microcephaly, and progressive diffuse cerebral atrophy. However, only a few cases have been reported in the literature and there is still a limited amount of information about the symptomatology and pathophysiology associated with pathogenic variants of DNM1L. We report a 10‐year‐old girl with a one‐year history of mild learning disorder and absence seizures who presented with new‐onset focal status epilepticus which progressed to severe encephalopathy and asymmetric hemispheric cerebral atrophy. Differential diagnosis included mitochondrial disease, Rasmussen's encephalitis, and autoimmune encephalitis. Disease progressed from one hemisphere to the other despite anti‐seizure medications, hemispherectomy, vagus nerve stimulator, ketogenic diet, and immunomodulators. Continued cerebral atrophy and refractory seizures evolved until death four years after initial presentation. Post‐mortem whole‐exome sequencing revealed a pathogenic DNM1L variant. This paper presents a novel case of adolescent‐onset DNM1L‐related intractable epilepsy and encephalopathy.     

Complex partial status epilepticus as a manifestation of Hashimoto''s encephalopathy

Epileptic seizures are a frequent manifestation of Hashimoto's encephalopathy. However, status epilepticus associated with Hashimoto's encephalopathy are not well characterized in medical literature. We described here a 16-year-old girl who presented with complex partial status epilepticus associated with elevated anti-thyroid antibodies. Ictal EEG showed lateralized high amplitude rhythmic delta waves over the right hemisphere and ictal single-photon emission computed tomography revealed regional hyperperfusion of the right parietal and temporal lobes. The patient was unresponsive to antiepileptic drug therapy but responded to intravenous steroid treatment. Screening of serum anti-thyroid antibodies for unexplained encephalopathy with epileptic seizures is suggested, as early recognition and prompt steroid treatment may lead to a favorable prognosis.     

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.     

Non‐convulsive status epilepticus in the elderly

Altered mental state is a very common presentation in the elderly admitted to the emergency department. It has been determined that about 16% of patients aged 60 or older with confusion of unknown origin have non‐convulsive status epilepticus. The diagnosis of non‐convulsive status epilepticus is difficult in the elderly because possible aetiologies of confusion may present with the same clinical picture. Non‐convulsive status epilepticus in the elderly carries major morbidity and mortality, attributable primarily to aetiology, and treatment is complex, involving treatment of the aetiology and concomitant medical illnesses, whilst balancing the side effects and drug interactions of antiepileptic drugs.     

Treatment responsive GABA(B)‐receptor limbic encephalitis presenting as new‐onset super‐refractory status epilepticus (NORSE) in a deployed U.S. soldier

A 23‐year‐old, previously healthy, deployed U.S. soldier presented with bilateral temporal lobe seizures recalcitrant to multiple antiepileptic drugs and anti‐seizure anaesthetic agents. He received methylprednisolone, intravenous immunoglobulins, plasma exchange, and rituximab for presumed autoimmune encephalitis before achieving seizure freedom. Six weeks after presentation, the aetiology of his refractory seizures was found to be due to autoantibodies targeting the anti‐GABA(B)‐receptor. This case is noteworthy for being the first reported case of anti‐GABA(B)‐receptor limbic encephalitis presenting with new‐onset refractory status epilepticus (NORSE), a clinical syndrome that often carries a grave prognosis and in which a treatable aetiology is often never discovered. Our case also supports testing for GABA‐receptor autoantibodies and the upfront use of multi‐modal immunotherapy in patients presenting with limbic encephalitis and new refractory seizures.     

MELAS with recurrent complex partial seizures,nonconvulsive status epilepticus,psychosis, and behavioral disturbances: Case analysis with literature review

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is a progressive neurodegenerative disorder associated with polygenetic, maternally inherited, mitochondrial DNA mutations. MELAS has multisystem presentation including neurological, muscular, endocrine, auditory, visual, cardiac, psychiatric, renal, gastrointestinal and dermatological symptoms. Clinical course and prognosis are variable, often leading to cognitive decline, disability, and premature death. Both convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) are reported with MELAS. This report illustrates a case of MELAS with recurrent complex partial seizures, NCSE, confusion, aggressive behaviors, hallucinations, and paranoid delusions. Rapid video/EEG confirmation of diagnosis and aggressive antiepileptic drug intervention are required. Further education of medical professionals regarding this disorder, its appropriate management, and the significance of NCSE is indicated to avoid delay of treatment.     

Effectiveness of multimodality treatment for autoimmune limbic epilepsy

We evaluated the outcome of multimodality treatment in autoimmune limbic epilepsy in 3 consecutive patients (2 male and 1 female; age 33–55 years) presenting with a combination of focal non‐convulsive status epilepticus, memory impairment, and psychosis. MRI showed right or bitemporal T2 or FLAIR hyperintensity. Video‐EEG showed seizures of right temporo‐occipital or bitemporal independent onset. Extensive workup failed to reveal infectious aetiology or an underlying tumour. However, the autoantibody panel was positive for one or more of these antibodies: anti‐VGKC, anti‐GABA_B, anti‐VGCC (P/Q, N types), and anti‐GAD65. All patients received: (1) conventional antiepileptic drugs including levetiracetam, lacosamide, phenobarbital, lamotrigine, and valproate; (2) immunomodulatory therapy including methylprednisolone, plasmapheresis, and intravenous immunoglobulin; and (3) rituximab. After a 4–6‐week in‐hospital course, the seizures resolved in all patients but 2 had persistent memory impairment. None had treatment‐related complications. At the time of last follow‐up, 2–3 months later, 2 patients remained seizure‐free while 2 had residual memory impairment. Our findings suggest that multimodality treatment with a combination of conventional AEDs, immunomodulatory therapy, and rituximab is effective and safe in autoimmune limbic epilepsy.     

Infectious disease or Hashimoto's encephalopathy flares: A case report

Hashimoto's encephalopathy is an under-recognized and rare disease that presents a diagnostic conundrum since many features are suggestive of infectious etiologies and yet treatment is immunosuppressive medications. We describe a case of a male with a history of recurrent seizures who presented with a subacute onset of confusion, persistent leukocytosis and fever while on immunosuppressant therapy, whose response to high dose steroids was incomplete and who achieved a complete remission of all symptoms when plasmapheresis was initiated. A negative cerebrospinal fluid (CSF) and serum microbiological testing in a patient with an abnormal EEG, increased CSF protein, and elevated thyroid antibodies should prompt consideration of Hashimoto's encephalopathy. If after treating with high dose steroids, there is a sub-optimal clinical response, plasmapheresis should be considered.     

以癫痫持续状态起病的桥本脑病1例分析

目的 探讨以癫痫持续状态为首发表现的桥本脑病的临床特征。方法 回顾性分析1例以癫痫持续状态为首发表现的桥本脑病患者的临床资料。结果 临床呈癫痫持续状态,入院时神志不清,间断抽搐伴瞳孔散大,间歇期仍昏迷,余无明显局灶定位体征; 血气pH值6.807,乳酸24 mmol/L,头颅CT、MRI检查均未见异常,2次腰穿脑脊液常规、生化均正常,自身免疫性脑炎抗体8项均阴性,甲状腺功能检测提示轻度甲减,抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体升高,诊断桥本脑病,给予丙种球蛋白及甲强龙冲击治疗后病情迅速并明显好转,用药次日患者神志转清楚,癫痫持续状态得到有效控制。结论 桥本脑病临床以癫痫持续状态为首发者少见,故遇到不明原因的脑病患者,需注意甲状腺功能及相关抗体检查,以尽快明确诊断,尽早治疗,最大程度地改善其预后。     

The use of levetiracetam in refractory status epilepticus.

Six patients with status epilepticus (SE) of various etiologies refractory to at least two antiepileptic drugs (AEDs) had complete cessation of their seizures following administration of oral levetiracetam (LEV). Seizure types included convulsive, focal, and nonconvulsive status epilepticus. Effective doses of levetiracetam ranged from 500 to 3000 mg/day, achieving seizure control within 12-96 h. No significant adverse events were noted. Adjunctive levetiracetam should be considered for patients with status epilepticus unresponsive to initial therapy.     

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.     

Status epilepticus as a manifestation of hepatic encephalopathy

OBJECTIVES: Seizures have been described as a rare manifestation of hepatic encephalopathy. MATERIAL AND METHODS: We present a 54-year-old female, with 6-year history of decompensated, hepatitis B liver cirrhosis, admitted with generalized seizures. She reported a history of recurrent episodes of hepatic encephalopathy, spontaneous bacterial peritonitis, tense ascites and variceal hemorrhage. Neurologic examination revealed a comatose patient, without papilledema. Laboratory examinations were suitable with cirrhosis and mild renal failure. Blood gas examination revealed severe metabolic acidosis and hypoxemia. Plasma NH3+ levels upon admission were twice normal. Brain computed tomography and magnetic resonance imaging were normal. Electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy, grades III-IV. RESULTS: Status epilepticus was refractory to continuous antiepileptic treatment. However, it was resolved after 24-h therapy with lactulose. Blood NH3 levels were simultaneously normalized with clinical improvement. CONCLUSIONS: We consider the status epilepticus of our patient to be a rare manifestation of hepatic encephalopathy.     

Non-convulsive status epilepticus of frontal origin as the first manifestation of Hashimoto's encephalopathy

Hashimoto's encephalopathy is an often misdiagnosed, life threatening, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto's encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a form of non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto's encephalopathy may lead to a favourable prognosis. [Published with video sequences].     

Palatal tremor, focal seizures, repeated miscarriages and elevated anti-thyroid antibodies

Neurological manifestations of thyroid autoimmunity are heterogeneous and nonspecific. The most frequently adopted name for this entity is Hashimoto's encephalopathy although this eponym has been recently contested. In the absence of specific clinical features, diagnosis is suggested by the presence of elevated levels of anti-thyroid antibodies in the appropriate clinical context. We describe a patient with recurrent focal seizures, palatal tremor and elevated anti-thyroid antibodies but no encephalopathy. Her past medical history was marked by recurrent miscarriages. The markedly elevated thyroid antibodies, the temporal relationship between neurological symptoms and hypothyroidism, and the absence of another explanation to her symptoms suggest a causal role of thyroid autoimmunity. In the clinical setting of recurrent spontaneous miscarriages, elevated levels of anti-thyroid antibodies and neurological deficits not attributed to another disease entity, Hashimoto's encephalopathy should be suspected.     

Avoiding anaesthetics after multiple failed drug‐induced comas: an unorthodox approach to management of new‐onset refractory status epilepticus (NORSE)

New‐onset refractory status epilepticus (NORSE) is a rare, poorly understood and often catastrophic condition. There is little guidance available for management. Here, we describe the course of a 19‐year‐old man with NORSE who was treated successfully with a new approach. Our patient was initially treated with first‐, second‐ and third‐line agents including a total of seven failed drug‐induced coma courses until the 30^th day of hospitalization. When withdrawal of care was contemplated, management was then assumed by dedicated epileptologists and treatment course was changed. An unorthodox decision was made to avoid IV anaesthetics unless there were generalized bisynchronous tonic‐clonic or generalized non‐convulsive (electrographic) seizures. This approach allowed real‐time assessment of treatment response to aggressive non‐sedating AED therapy while the multifocal convulsive and non‐convulsive seizures were ongoing. It also eliminated potentially fatal IV anaesthetic‐induced complications and prevented anaesthetic withdrawal seizures. This was effective in achieving full recovery in our patient. The patient's awakening also changed the perspective of family members and care providers, avoiding premature withdrawal of care, which is often the cause of death in similar patients.     

A case of recurrent status epilepticus and successful management with progesterone

Catamenial epilepsy (CE) is a commonly observed phenomenon among women with epilepsy, the management of which is both hormonal and non‐hormonal. Progesterone therapy has been tried in these patients, as the possible mechanism of CE is withdrawal of progesterone and a higher oestrogen/progesterone ratio in the perimenstrual and periovulatory periods. Here, we describe a 24‐year‐old lady with multiple seizure types since childhood, which were refractory to adequate antiepileptic drug therapy after menarche with catamenial clustering of seizures. She went on to have several episodes of non‐convulsive status epilepticus also with similar periodicity, which would abate only with midazolam infusion, without the need for ventilatory support. She was tried on acetazolamide, progesterone vaginal pessaries, and maximum tolerated doses of antiepileptic medications, but finally responded to intramuscular and oral progesterone, and has been seizure‐free for more than a year.     

Hashimoto encephalopathy: literature review

Hashimoto encephalopathy (HE) presents as an encephalopathy without central nervous system infection or tumor. HE is associated with autoimmune thyroiditis and is thus considered to be an autoimmune disorder. The prevalence of HE is low, but death and status epilepticus have been reported. HE manifests with a wide range of symptoms that include behavioral changes and confusion. Elevated thyroid antibodies are present in the majority of cases and are required for the diagnosis of HE. Normal brain MRI findings are found in the majority of patients diagnosed with HE. The most consistent CSF abnormality noted in HE patients is the presence of elevated protein. Most HE patients respond well to steroid therapy. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis. In conclusion, it is now generally accepted that the diagnosis of HE must include encephalopathy characterized by cognitive impairment associated with psychiatric features, such as hallucinations, delusions, and paranoia. Autoimmune encephalitis and prion disease should be considered in the differential diagnosis due to the similarity of the clinical features of these conditions to those of HE.     

Tonic status epilepticus in a centenarian woman

Generalized tonic status epilepticus (TSE) is a rare epileptic condition. It occurs usually in the context of symptomatic generalized epilepsy, in particular, in subjects with a diagnosis of Lennox‐Gastaut syndrome, atypical forms of idiopathic (genetic) generalized epilepsy, or as a paradoxical effect during treatment with diverse antiepileptic drugs. Herein, we describe the case of an elderly woman on chronic treatment with psychotropic drugs who developed an episode of generalized TSE. Motor manifestations were subtle and difficult to recognize as seizures, and a detailed video‐EEG importantly contributed to accurate and prompt diagnosis. TSE was initially refractory to conventional anti‐seizure drug therapy including levetiracetam and valproate but was finally controlled with lacosamide. Our case indicates a potential therapeutic effect of lacosamide on TSE in the elderly after treatment failure with first‐line anti‐seizure drugs. [Published with video sequence on www.epilepticdisorders.com ]