The diagnosis of idiopathic paroxysmal kinesigenic dyskinesia (PKD) can be made based on historical features. The correct diagnosis has implications for treatment and prognosis, and the diagnostic scheme may allow better focus in the search for the PKD gene(s).

Summary Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions (PKD/IC) is an episodic movement disorder with autosomal dominant inheritance and high penetrance, but the causative gene is unknown. We have now identified four truncating mutations involving the PRRT2 gene in the vast majority (24/25) of well characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. The PRRT2 gene encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture and mutants associated with PKD/IC lead to dramatically reduced PRRT2 protein levels leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated by alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD in 50 individuals from eight families. The mutations cause changes (Ala to Val) in the N-terminal region of two MR-1 isoforms. The MR-1L isoform is specifically expressed in brain and is localized to the cell membrane while the MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress. Our results suggest a mechanism whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD. Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias.

Paroxysmal nonkinesigenic dyskinesia (PNKD) should be strictly defined based on age at onset and ability to precipitate attacks with caffeine and alcohol. Patients with this clinical presentation (which is similar to the phenotype initially reported by Mount and Reback) are likely to harbor myofibrillogenesis regulator 1 (MR-1) gene mutations. Other "PNKD-like" families exist, but atypical features suggests that these subjects are clinically distinct from PNKD and do not have MR-1 mutations. Some may represent paroxysmal exertional dyskinesia.

Several human neuroimaging studies have reported activity in the precentral gyrus (PcG) ipsilateral to the side of hand movements. This activity has been interpreted as the part of the primary motor cortex (M1) that controls bilateral or ipsilateral hand movements. To better understand hand ipsilateral-PcG activity, we performed a functional MRI experiment in eight healthy right-handed adults. Behavioral tasks involved hand or lower face movements on each side or motor imagery of the same movements. Consistent with the known M1 organization, the hand contralateral-PcG activity was centered at the "hand-knob" portion of the PcG; face contralateral-PcG activity was localized ventrolateral to it. Hand ipsilateral-PcG activity was identified in most subjects. However, converging results indicated that this ipsilateral PcG activity was situated in Brodmann's area 6 in both hemispheres. The hand ipsilateral-PcG zones were active not only during hand movements but also face movements. Moreover, the hand ipsilateral-PcG zones revealed substantial imagery-related activity, which also failed to differentiate the hand and face. Statistical analyses confirmed poor effector selectivity of the hand ipsilateral PcG activity during both movement and imagery tasks. From these results, we conclude that the hand ipsilateral-PcG activity in healthy adults probably corresponds to a part of the ventral premotor cortex. In contrast, available evidence suggests that M1 contributes to controlling the ipsilateral hand in children and patients after stroke recovery. It appears that within the human PcG, there are two parallel systems potentially capable of controlling ipsilateral hand movements: ventral premotor cortex and M1. These two systems may be differentially influenced by developmental or pathologic changes.

Understanding the multiple etiologic mechanisms that produce optic disc swelling in sarcoidosis can help neurologists tailor treatment for patients with neurosarcoidosis who present with this symptom.

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Anti-glutamic acid decarboxylase (GAD) antibody-associated autoimmune encephalitis has been reported mostly as limbic encephalitis. Only few cases with extralimbic involvement are reported with limited investigation. Here, we report an extensive investigation with MRI, PET, and pathological examination. A 66-year-old Japanese female with a history of hypothyroidism, colon cancer, pheochromocytoma, and thymoma-associated myasthenia gravis presented with generalised tonic-clonic seizures. MRI showed multiple hyperintense lesions and PET showed hypermetabolic lesions in the brain. Biopsy showed non-specific gliosis, microglial proliferation, and perivascular lymphohistiocytic infiltrates. Various neuronal antibodies were negative, except for anti-GAD antibody. Anti-GAD antibody-associated encephalitis is an increasingly recognised CNS disease. Pathophysiology of this encephalitis is unclear. While PET showed hypermetabolic lesions, the biopsy showed non-specific changes. The treatments may include immunosuppressants, IVIg, and plasma exchange. One should consider to measure this antibody, in addition to others, when autoimmune encephalitis is suspected [Published with video sequences].