Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex.

Medically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long-term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality.

Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy.

Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

Anterior nucleus of the thalamus: functional organization and clinical implications.

The anterior nucleus of thalamus (ANT) is a key component of the hippocampal system for episodic memory. The ANT consist of 3 subnuclei with distinct connectivity with the subicular cortex, retrosplenial cortex, and mammillary bodies. Via its connections with the anterior cingulate and orbitomedial prefrontal cortex, the ANT may also contribute to reciprocal hippocampal-prefrontal interactions involved in emotional and executive functions. As in other thalamic nuclei, neurons of the ANT have 2 different state-dependent patterns of discharge, tonic and burst-firing; some ANT neurons also contribute to propagation of the theta rhythm, which is important for mechanisms of synaptic plasticity of the hippocampal circuit. Clinical and experimental evidence indicate that damage of the ANT or its inputs from the mammillary bodies are primarily responsible for the episodic memory deficit observed in Wernicke-Korsakoff syndrome and thalamic stroke. Experimental models also indicate that the ANT may have a role in the propagation of seizure activity both in absence and in focal seizures. Because of its central connectivity and possible role in propagation of seizure activity, the ANT has become an attractive target for deep brain stimulation (DBS) for treatment of medically refractory epilepsy. The ANT is one of the nuclei preferentially affected in prion disorders, such as fatal familial insomnia, but the relationship between ANT involvement and the clinical manifestations of these disorders remains unclear. The connectivity patterns and electrophysiology of the ANT have been the subject of several reviews.(1-4.)

Mystery case: Cowden syndrome presenting with partial epilepsy related to focal cortical dysplasia.

A 55-year-old man presented with seizures characterized by "tightening" of the right side and variable loss of awareness. EEG showed focal epileptogenic abnormalities over left and midline central regions. MRI showed left frontal focal cortical dysplasia (figure 1). He had multiple skin lesions (figure 2) and colonoscopy revealed gastrointestinal mucosal ganglioneuromas. Genetic testing of PTEN gene confirmed a diagnosis of Cowden syndrome (CS).

Amyloid-ß-related angiitis presenting as a uveomeningeal syndrome.

A 59-year-old man had a 2-month history of nonfluctuating encephalopathy. He initially presented acutely with fevers, headaches, and word-finding difficulties. The sedimentation rate was elevated with a bland CSF and normal MRI head. Body CT showed diffuse pulmonary interstitial thickening with patchy opacification. Following treatment for pneumonia, there was resolution of fevers. No infectious etiology was identified. Within days of discharge, he developed bilateral uveitis, which was successfully treated with corticosteroid eyedrops and oral acyclovir. One month later, he developed confusion and unsteadiness. Repeat MRI was reportedly normal; body CT showed resolution of lung changes but diffuse lymphadenopathy persisted. A lymph node biopsy, reviewed at our institution, showed nonspecific reactive changes and fibrosis. Due to progressive encephalopathy and worsening headaches 2 months after symptom onset, the patient presented to our institution. On examination, he scored 30/38 on the Kokmen short test of mental status,(1) losing points for attention and immediate and delayed recall. Funduscopy revealed bilateral disc edema. He had mild appendicular ataxia and impaired tandem walk. The remainder of the examination was normal.