General symptoms[edit] => In one of the few reported cases, the subject presented with muscle weakness and fatigue, muscle twitching, excessive sweating and salivation, small joint pain, itching and weight loss. The subject also developed confusional episodes with spatial and temporal disorientation, visual and auditory hallucinations, complex behavior during sleep and progressive nocturnal insomnia associated with diurnal drowsiness. There was also severe constipation, urinary incontinence, and excessive lacrimation. When left alone, the subject would slowly lapse into a stuporous state with dreamlike episodes characterized by complex and quasi-purposeful gestures and movements (enacted dreams). Marked hyperhidrosis and excessive salivation were evident. Neurological examination disclosed diffuse muscle twitching and spontaneous and reflex myoclonus, slight muscle atrophy in the limbs, absence of tendon reflexes in the lower limbs and diffuse erythema especially on the trunk with scratching lesions of the skin.[4] Compulsive behaviours, stereotypies and reduplicative paramnesias can be part of the CNS spectrum.[7]
Insomnia[edit] => In all of the reported cases, the need for sleep was severely reduced and in some cases not necessary. The duration of sleep in one case decreased to about 2–4 hours per 24-hour period.[8] Clinical features pertaining to insomnia include daytime drowsiness associated with a loss of ability to sleep, intermingled with confusional oneiric status, and the emergence of atypical REM sleep from wakefulness. The Polysomnogram (PSG) picture of this disease is characterized by an inability to generate physiological sleep (key features are the suppression of the hallmarks of stage 2 non-REM sleep: spindles and K complexes) and by the emergence of REM sleep without atonia. The involvement of the thalamus and connected limbic structures in the pathology indicate the prominent role that the limbic thalamus plays in the pathophysiology of sleep.[3] In a case documented in 1974, PSG findings documented the sustained absence of all sleep rhythms for up to a period of 4 months.[5]
Electroencephalography (EEG) in one case was dominated by "wakefulness" and “subwakefulness” states alternating or intermingled with short (< 1 min) atypical REM sleep phases, characterized by a loss of muscle atonia. The “subwakefulness” state was characterized by 4–6 Hz theta activity intermingled with fast activity and desynchronized lower voltage theta activity, behaviourally associated with sleep-like somatic and autonomic behavior. The subject was said to suffer from “agrypnia excitata”, which consists of severe total insomnia of long duration associated with decreased vigilance, mental confusion, hallucinations, motor agitation, and complex motor behavior mimicking dreams, and autonomic activation. CNS and autonomic symptoms were caused by impaired corticolimbic control of the subcortical structures regulating the sleep-wake and autonomic functions.[4]
Neuromyotonia[edit] => Neuromyotonia refers to muscle twitching and cramping at rest that is exacerbated with exercise. It is caused by sustained or repetitive spontaneous muscle activity of peripheral nerve origin. Myokymia, or spontaneous rippling and twitching movements of muscles, is a visible component of neuromyotonia. Electromyography (EMG) discloses spontaneous, repetitive motor unit or single fiber discharges firing in irregular rhythmic bursts at high intraburst frequencies.[1] Some of the muscles exhibiting twitching include the bilateral gastrocnemii, quadriceps femoris, biceps brachii, and right masseter.[8] In vivo electrophysiological studies suggest at least some dysfunction of the muscle cell membrane.[6] In the examined muscles, no abnormal insertional activity or fibrillation potentials were noted. Nerve conduction studies were normal.[4]
Other symptoms[edit] => Breathing difficulties can occur, resulting from neuromyotonic activity of the laryngeal muscles. Laryngeal spasm possibly resulting from neuromyotonia has been described previously, and this highlights that, in patients with unexplained laryngospasm, neuromytonia should be added to the list of differential diagnoses.[6]
Studies have shown subtly decreased metabolism on positron emission tomography (PET) and single photon emission computed tomography (SPECT) in the left inferior frontal and left temporal lobes.[8] and or basal ganglia hypermetabolism.[7] Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus.[9]
Cerebral spinal fluid (CSF) shows normal protein, glucose, white blood cell, and IgG index but there are weak oligoclonal bands, absent in the blood. Marked changes in circadian serum levels of neurohormones and increased levels of peripheral neurotransmitters were also observed. The absence of morphological alterations of the brain pathology, the suggestion of diffusion of IgG into the thalamus and striatum, more marked than in the cortex (consistent with effects on the thalamolimbic system) the oligoclonal bands in the CSF and the amelioration after PE all strongly support an antibody-mediated basis for the condition.[4] Raised CSF IgG concentrations and oligoclonal bands have been reported in patients with psychosis. Anti-acetylcholine receptors (anti-AChR) antibodies have also been detected in patients with thymoma, but without clinical manifestations of myasthenia gravis.[1] There have also been reports of non-paraneoplastic limbic encephalitis associated with raised serum VGKC suggesting that these antibodies may give rise to a spectrum of neurological disease presenting with symptoms arising peripherally, centrally, or both. Yet, in two cases, oligoclonal bands were absent in the CSF and serum, and CSF immunoglobulin profiles were unremarkable.[2]