Epilepsia partialis continua: A review.

Epilepsia partialis continua (EPC) is a rare type of focal motor seizure characterized by continuous, involuntary muscle contractions in a specific part of the body. These contractions usually involve rhythmic, twitching movements and can last for several hours to days. The seizures are usually limited to one part of the body and can be clonic or dystonic. EPC can affect people of all ages but is more common in children and adolescents. The pathophysiology of EPC is complex and depends on the cause. There are several possible causes of EPC including structural brain abnormalities, infections, metabolic and genetic disorders, inflammatory conditions, traumatic brain injury, and vascular causes. The work-up of EPC includes electroencephalography (EEG), magnetic resonance imaging (MRI) of the brain, position emission tomography (PET) scan of the brain, autoimmune antibodies, infection work-up, and metabolic and genetic work-up. The management of EPC can be challenging. Antiseizure medications (ASDs) including benzodiazepines are an integral part of the management of EPC. Immunotherapy trials are recommended in resistant cases. Epilepsy surgery is one of the effective modalities in some surgically amenable cases. This article reviews the topic of EPC and summarizes diagnostic and .treatment recommendations.

Anti-GABA-A Receptor Antibody-Mediated Epilepsia Partialis Continua After Treatment With Alemtuzumab: A Case Report.

BACKGROUND AND OBJECTIVES: Patients with anti-GABA-A receptor encephalitis characteristically experience therapy-refractory epileptic seizures. General anesthesia is often required to terminate refractory status epilepticus. The immunologic mechanisms leading to antibody formation remain to be elucidated. Described triggers of anti-GABA-A autoimmunity are tumors, mainly thymomas, and herpes simplex encephalitis. METHODS: We present a young woman with prediagnosis of relapse remitting multiple sclerosis (MS), treated with interferons, natalizumab, and alemtuzumab. Six months after one and only cycle of alemtuzumab, speech arrest and behavioral changes with aggressive and anxious traits appeared. She showed increasing motor convulsions resulting in focal status epilepticus. RESULTS: Anti-GABA-A receptor antibodies in CSF and serum were confirmed in different external laboratories, in a more extensive analysis after antibodies against NMDAR, CASPR2, LGI1, GABABR, and AMPAR were ruled out during in-house examination. Clinical condition improved temporarily with cortisone therapy, plasmapheresis, and IVIG but deteriorated rapidly after steroid discontinuation, resulting in brain biopsy. On histopathologic confirmation consistent with anti-GABA-A receptor antibody-associated CNS inflammation, completing the first rituximab cycle, continuing oral corticosteroids and supplementing immunosuppression with cyclosporine A led to quick recovery. DISCUSSION: Our case describes a severe autoantibody-induced encephalitis in a young patient with MS, with alemtuzumab as a potential trigger for anti-GABA-A receptor encephalitis.

Responsive neurostimulation for focal motor status epilepticus.

No clear evidence-based treatment paradigm currently exists for refractory and super-refractory status epilepticus, which can result in significant mortality and morbidity. While patients are typically treated with antiepileptic drugs and anesthetics, neurosurgical neuromodulation techniques can also be considered. We present a novel case in which responsive neurostimulation was used to effectively treat a patient who had developed super-refractory status epilepticus, later consistent with epilepsia partialis continua, that was refractory to antiepileptic drugs, immunomodulatory therapies, and transcranial magnetic stimulation. This case demonstrates how regional therapy provided by responsive neurostimulation can be effective in treating super-refractory status epilepticus through neuromodulation of seizure networks.

Infantile epilepsy with multifocal myoclonus caused by TBC1D24 mutations.

PURPOSE: To summarize the clinical features and neuroimaging changes of epilepsy associated with TBC1D24 mutations. METHODS: Genetic testing was conducted in all epilepsy patients without acquired risk factors for epilepsy. Epilepsy patients identified with TBC1D24 compound heterozygous mutations by next-generation sequencing (NGS) epilepsy panel or whole exome sequencing (WES) were enrolled. The enrolled patients were followed up to summarize the clinical features. RESULTS: Nineteen patients were identified with TBC1D24 compound heterozygous mutations. Nine patients carried the same pathogenic variant c.241_252del. The seizure onset age ranged from 1 day to 8 months of age (median age 75 days). The most prominent features were multifocal myoclonus and epilepsia partialis continua (EPC). Myoclonus could be triggered by fever or infection in 15 patients, and could be terminated by sleep or sedation drugs. Psychomotor developmental delay was presented in 11 patients. Six patients exhibited hearing loss. Brain MRIs were abnormal in eight patients. Twelve patients were diagnosed with epilepsy syndromes including one patient who was diagnosed with Dravet syndrome. Two patients died due to status epilepticus at 4 months and 19 months of age, respectively. CONCLUSION: TBC1D24 mutation related epilepsy was drug-resistant. Multifocal myoclonus, EPC, and fever-induced seizures were common clinical features. Most patients presented psychomotor developmental delay. The neuroimaging abnormality and hearing loss could exacerbate during follow-up.

Comparative analysis of explanted DBS electrodes.

BACKGROUND: Hardware-related complications frequently occur in deep brain stimulation. Microscopy and spectroscopy techniques are effective methods for characterizing the morphological and chemical basis of malfunctioning DBS electrodes. A previous report by our team revealed the morphological and chemical alterations on a malfunctioning explanted electrode when it was compared to a new device. The aim of this preliminary study was to verify whether these morphological and chemical alterations in the materials were a direct result of the hardware malfunctioning or if the failure was correlated to a degradation process over time. METHODS: Two DBS electrodes were removed from two patients for reasons other than DBS system impairment and were analyzed by a scanning electron microscope and by an energy-dispersive X-ray spectroscopy. The results were compared to a malfunctioning device and to a new device, previously analyzed by our group. RESULTS: The analysis revealed that the wear of the polyurethane external part of all the electrodes was directly correlated with the duration of implantation period. Moreover, these alterations were independent from the electrodes functioning and from parameters used during therapy. CONCLUSIONS: This is the first study done that demonstrates a time-related degradation in the external layer of DBS electrodes. The analyses of morphological and chemical properties of the implanted devices are relevant for predicting the possibility of hardware's impairment as well as to improve the bio-stability of DBS systems.

Epilepsia partialis continua responsive to neocortical electrical stimulation.

Epilepsia partialis continua (EPC), defined as a syndrome of continuous focal jerking, is a rare form of focal status epilepticus that usually affects a distal limb, and when prolonged, can produce long-lasting deficits in limb function. Substantial electrophysiologic evidence links the origin of EPC to the motor cortex; thus surgical resection carries the risk of significant handicap. We present two patients with focal, drug-resistant EPC, who were admitted for intracranial video-electroencephalography monitoring to elucidate the location of the epileptogenic focus and identification of eloquent motor cortex with functional mapping. In both cases, the focus resided at or near eloquent motor cortex and therefore precluded resective surgery. Chronic cortical stimulation delivered through subdural strips at the seizure focus (continuous stimulation at 60-130 Hz, 2-3 mA) resulted in >90% reduction in seizures and abolition of the EPC after a follow-up of 22 months in both patients. Following permanent implantation of cortical stimulators, no adverse effects were noted. EPC restarted when intensity was reduced or batteries depleted. Battery replacement restored previous improvement. This two-case report opens up avenues for the treatment of this debilitating condition.

Vagus nerve stimulation for drug-resistant Epilepsia Partialis Continua: report of four cases.

BACKGROUND: Vagus nerve stimulation (VNS) represents an adjunctive surgical option for adult and pediatric patients with drug-resistant epilepsy, who are not eligible for surgical resection or disconnection. However, little is known on its efficacy in the treatment of Epilepsia Partialis Continua (EPC), a rare but serious form of motor status epilepticus associated either with progressive or with non-evolving neurological diseases. PURPOSE AND METHODS: To evaluate the effect of VNS in a series of four children affected by medically unresponsive EPC secondary to chronic inflammatory encephalopathy (two cases), Rasmussen encephalitis (one case) and poliodystrophy (one case). RESULTS: After VNS implantation, the stimulation amplitude was progressively increased and, after a mean interval of 47 days, a partial reduction of EPC and associated focal seizures was observed in all patients. After a mean follow-up of three years, one child stopped EPC, two presented short and rare episodes and in one patient 2-3 residual seizures per day was reported. In all cases, reduction of epileptic activity was associated with mild improvement of motor and cognitive abilities. No serious side effects were reported. CONCLUSION: VNS may be considered as an option for EPC when medical treatment fails and other more invasive neurosurgical options are not feasible.

Clinical course and variability of non-Rasmussen, nonstroke motor and sensory epilepsia partialis continua: a European survey and analysis of 65 cases.

PURPOSE: To gain new insights into the clinical presentation, causes, treatment and prognosis of epilepsia partialis continua (EPC), and to develop hypotheses to be tested in a prospective investigation. METHODS: In this retrospective multicenter study, all cases were included that fulfilled these criteria: constantly repeated fragments of epileptic seizures, with preserved consciousness, lasting ≥ 1 h and representing locally restricted motor or sensory epileptic activity. Single episodes were included when they lasted for a minimum of 1 day. EPC with Rasmussen syndrome and acute stroke were excluded. KEY FINDINGS: Three time courses with two subtypes each were distinguished, that is, EPC as a solitary event (de novo or in preexistent epilepsy); chronic repetitive nonprogressive EPC (with frequent or rare episodes); and chronic persistent nonprogressive EPC (primarily or evolving out of an episodic course). These were unrelated to etiologies (morphologic lesions 34%, inflammatory 29%, systemic disorders 9%, idiopathic 5%, unknown 23%). Precipitation and inhibition of seizures is a frequent feature of EPC. Levetiracetam and topiramate have improved the possibilities for pharmacotherapy. Topiramate seems to be particularly effective with dysontogenetic etiologies. SIGNIFICANCE: The existence of several clearly distinct courses of nonprogressive EPC is a new finding. These distinctions will be further investigated in a prospective study with precise protocols for electroencephalography (EEG), imaging, and other studies. This should better establish the relation of motor and somatosensory EPC; further clarify the relations, pathogenesis, and significance of the different types and their etiologies; and possibly identify more semiologic variants. It should also provide more precise knowledge about therapy and modification of ictogenesis by external stimuli.

Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a technique for noninvasive focal brain stimulation by which small intracranial electrical currents are generated by a fluctuating extracranial magnetic field. In clinical epilepsy, rTMS has been applied most often interictally to reduce seizure frequency. Less often, rTMS has been used to terminate ongoing seizures, as in instances of epilepsia partialis continua (EPC). Whether ictal rTMS is effective and safe in the treatment of EPC has not been extensively studied. Here, we describe our recent experience with rTMS in the treatment of EPC, as an early step toward evaluating the safety and efficacy of rTMS in the treatment of intractable ongoing focal seizures. METHODS: Seven patients with EPC of mixed etiologies were treated with rTMS applied over the seizure. rTMS was delivered in high-frequency (20-100 Hz) bursts or as prolonged low-frequency (1 Hz) trains. The EEG was recorded for three of the seven patients. RESULTS: rTMS resulted in a brief (20-30 min) pause in seizures in three of seven patients and a lasting (>or=1 day) pause in two of seven. A literature search identified six additional reports of EPC treated with rTMS where seizures were suppressed in three of six. Seizures were not exacerbated by rTMS in any patient. Generally mild side effects included transient head and limb pain, and limb stiffening during high-frequency rTMS trains. CONCLUSIONS: Our clinical observations in a small number of patients suggest that rTMS may be safe and effective in suppressing ongoing seizures associated with EPC. However, a controlled trial is needed to assess the safety and anticonvulsive efficacy of rTMS in the treatment of EPC.

Health and non-health care resources use in the management of adult outpatients with drug-resistant epilepsy in Spain: a cost-of-illness study (LINCE study).

PURPOSE: The purpose of this study was to ascertain health care and non-health care resources use in the past 12-months and to estimate the cost-of-illness in adult outpatients with drug-resistant epilepsy (DRE) in Spain. METHODS: A cross-sectional and retrospective study was designed. Whole nation representative participants (epilepsy and general neurological clinics) were selected at random, but patients with drug-resistant epilepsy were included consecutively. We choose the societal perspective to compute total costs for this study. Estimation of costs was calculated by multiplying unitary costs by number of resources used. RESULTS: Seven hundred sixty-two consecutive patients (50.8% males) with mean (S.D.) age of 40.5 (13.5) years were included. Mean total yearly costs were euro6838 (euro8100) with health costs of euro4977 (euro6490), and indirect costs of euro1618 (euro4527). Gender and severity of seizures were significantly associated with costs; higher in males and subjects with severe seizures. Total annual costs showed a trend toward statistical significant association with age (lower costs in older patients), but costs were unrelated with level of care in Epilepsy or general neurological clinics. DISCUSSION: Health care, and to a lesser extend non-health care resources use, were high in patients with DRE in Spain, yielding a considerable burden to both the National Health System and the Society. Better planning of therapeutic strategies allowing alleviation of load and costs of this health problem should be considered from these findings.

Transient suppression of seizures by repetitive transcranial magnetic stimulation in a case of Rasmussen's encephalitis.

Repetitive transcranial magnetic stimulation (rTMS) has been applied with variable success to terminate the seizures of epilepsia partialis continua. The rationale for using this technique to suppress ongoing seizures is the capacity of rTMS to interrupt ongoing neuronal activity, and to produce a lasting decrease in cortical excitability with low-frequency (1 Hz) stimulation. We report a case of epilepsia partialis continua in a child with Rasmussen's encephalitis, in whom seizures were transiently suppressed by 1-Hz rTMS delivered in nine daily 30-minute sessions. In this case, total ictal time was significantly reduced during stimulation, but the daily baseline seizure rate remained unchanged. Notably, the detection and quantification of this short-lived improvement were enabled by recording EEG continuously during the rTMS session. Thus, we present this case to illustrate a potential utility of combined continuous EEG recording and rTMS in seizure treatment.

Low-frequency transcranial magnetic stimulation for epilepsia partialis continua due to cortical dysplasia.

The potential therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in epilepsy has been increasingly recognized. We investigated the effects of low-frequency rTMS in a patient with epilepsia partialis continua (EPC) due to cortical dysplasia. A 31-year-old female patient experienced EPC in the right upper and lower extremities, which had lasted for 15 years without generalized seizures. MRI showed focal megaencephaly around the motor cortex suggestive of cortical dysplasia. A figure of eight magnetic coil was placed over the hand motor area, and 100 stimuli with an intensity at 90% of motor threshold were given at 0.5 Hz. Immediately after rTMS, EPC was nearly abolished. The effects had continued approximately for 2 months, and the second trial resulted in the similar effects and time-course. Low-frequency rTMS was safe and well tolerated in this patient. These findings support the concept that rTMS decreases cortical excitability, and may be an effective treatment for focal partial seizures.

Paraneoplastic recurrent multifocal encephalitis presenting with epilepsia partialis continua.

We report a 46-year-old female patient in whom epilepsia partialis continua was the initial presentation of small cell lung cancer. Magnetic resonance imaging revealed multiple, bilateral cortical lesions, which were originally misinterpreted and treated as brain metastases. Intracranial lesions and neurological symptoms remitted after corticosteroids, chemotherapy, and radiotherapy. After an asymptomatic interval of 18 months, neurological symptoms recurred with more extensive involvement of completely different parts of the central nervous system (limbic, brainstem and cerebellar structures) without any evidence of tumor recurrence. Both episodes showed a distinctive response to immunosuppressive therapy. The diagnostic challenges of the highly variable clinical presentations and therapeutic approaches to paraneoplastic multifocal encephalitis are discussed with relevant literature review.

Electroconvulsive therapy and repetitive transcranial magnetic stimulation in children and adolescents: a review and report of two cases of epilepsia partialis continua.

Brain stimulation for the treatment of psychiatric disorders has received increasing attention over the past decade. The introduction of experimental means to stimulate the brain noninvasively with magnetic fields not only has raised interest in these novel means of modulating brain activity but also has refocused attention on a mainstay in the treatment of severe major depression and other disorders (electroconvulsive therapy). This article reviews the current state of knowledge concerning the use electroconvulsive therapy, repetitive transcranial magnetic stimulation, and magnetic seizure therapy in children and adolescents. Two cases of medically intractable epilepsia partialis continua are presented to add to the limited literature on the use of repetitive transcranial magnetic stimulation in children and adolescents and illustrate the concept of using functional neuroimaging results to target the application of a focal intervention in an attempt to dampen hyperactive regions of the cortex.

rTMS reduces focal brain hyperperfusion in two patients with EPC.

OBJECTIVE: This study was performed to evaluate the acute effect of a single repetitive transcranial magnetic stimulation (rTMS) session in a focal hyperperfusion epileptogenic region to induce a transitory decrease of epileptiform activity. CASE REPORT: Two epilepsia partialis continua (EPC)-diagnosed patients, received one session with 15 trains of rTMS (20 Hz; 2 s train, inter-train of 58 s). Before rTMS session, a brain ictal single photon emission computed tomography (SPECT) was performed to localize the focal frontal hyperperfusion region to establish the stimulation site. Immediately after the rTMS session another ictal SPECT was performed. Both patients showed a decrease of perfusion in the stimulated regions. For patient 1 epileptic seizures became intermittent until they stopped in the following 24 h. Patient 2 showed only a minimal improvement with a frequency decrease of epileptic spikes. CONCLUSIONS: Our findings suggest that a single rTMS session reduces focal epileptogenic activity and could be an alternative approach for epileptic-resistant patients, but efficacy should be confirmed in a larger series.