Editing Morvan's syndrome (section)

==Signs and symptoms==

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.<ref name=cardiac/>
Compulsive behaviours, stereotypies and reduplicative paramnesias can be part of the CNS spectrum.<ref name="Spinazzi">Spinazzi M, Argentiero V, Zuliani L, Palmieri A, Tavolato B, Vincent A. Immunotherapy-reversed compulsive, monoaminergic, circadian rhythm disorder in Morvan syndrome. Neurology. 2008 9;71:2008-10.</ref>

===Insomnia===
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.<ref name=indian/>  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 [[Rapid eye movement sleep|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.<ref name=oneiricisms/>  In a case documented in 1974, PSG findings documented the sustained absence of all sleep rhythms for up to a period of 4 months.<ref name=agrypnia/>

[[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&nbsp;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 have “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.<ref name=cardiac/>

===Neuromyotonia===
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.<ref name=paraneoplastic/> Some of the muscles exhibiting twitching include the bilateral [[gastrocnemius muscle|gastrocnemii]], [[quadriceps femoris]], [[biceps brachii]], and right [[masseter]].<ref name=indian/>  [[In vivo]] electrophysiological studies suggest at least some dysfunction of the muscle [[cell membrane]].<ref name=clinical/>  In the examined muscles, no abnormal insertional activity or [[fibrillation]] potentials were noted.  Nerve conduction studies were normal.<ref name=cardiac/>

===Other symptoms===
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.<ref name=clinical/>

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 lobe]]s.<ref name=indian/> and or basal ganglia hypermetabolism.<ref name="Spinazzi"/> Ancillary laboratory tests including [[MRI]] and brain biopsy have confirmed temporal lobe involvement.  Cranial MRI shows increased signal in the [[hippocampus]].<ref name=thymoma/>

[[Cerebral spinal fluid]] (CSF) shows normal protein, [[glucose]], [[white blood cell]], and [[immunoglobulin G]] (IgG) levels, but there are weak [[oligoclonal bands]], which are absent in the [[Serum (blood)|blood serum]].  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.<ref name=cardiac/> 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]].<ref name=paraneoplastic/>  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.<ref name=sub-acute/>

===Comorbid conditions===
In one case, a patient was diagnosed with both Morvan's syndrome and pulmonary hyalinizing granulomas (PHG). PHG are rare fibrosing lesions of the lung, which have central whorled deposits of lamellar [[collagen]].  How these two diseases relate to one another is still unclear.<ref>{{cite journal|title=Radiology-Pathology Conference: pulmonary hyalinizing granuloma associated with lupus-like anticoagulant and Morvan's Syndrome|journal=Clinical Imaging|date=2007-03-26|first=David I.|last=Winger |author2=Peter Spiegler |author3=Terence K. Trow|volume=31|issue=4|pages=264–268|doi=10.1016/j.clinimag.2007.03.007|pmid=17599621 |display-authors=etal}}</ref>

Thymoma, [[prostate]] adenoma, and in situ [[carcinoma]] of the [[sigmoid colon]] have also been found in patients with Morvan's Syndrome.<ref name=paraneoplastic/>