Morvan's syndrome
Encyclopedia
Morvan’s Syndrome, or Morvan’s fibrillary chorea (MFC), is a rare autoimmune disease named after nineteenth century French physician Augustin Marie Morvan
. “La chorée fibrillaire” was first coined by Morvan in 1890 when describing patients with multiple, irregular contractions
of the long muscles, cramping, weakness, pruritus, hyperhidrosis
, insomnia
, and delirium
.
It normally presents with a slow insidious onset over months to years.
Approximately 90% of cases spontaneously go into remission, while the other 10% of cases lead to death.
(muscle twitching) associated with muscle pain, excessive sweating, and disordered sleep.
This rare disorder is characterized by severe insomnia, amounting to no less than complete lack of sleep (agrypnia) for weeks or months in a row, and associated with autonomic alterations consisting of profuse perspiration with characteristic skin Miliaria
(miliaria rubra, sweat rash or prickly heat), tachycardia
, increased body temperature, and hypertension
. Patients display a remarkable hallucinatory behavior, and peculiar motor disturbances, which Morvan reported under the term “fibrillary chorea” but which are best described nowadays as neuromyotonic discharges.
The association of the disease with thymoma, tumour, autoimmune diseases, and autoantibodies suggests an autoimmune or paraneoplastic aetiology. Besides an immune-mediated etiology
, it is also believed to occur in gold, mercury, or manganese poisoning.
With only a limited number of reported cases, the complete spectrum of the Central Nervous System
(CNS) symptomatology has not been well established.
The natural history of Morvan’s is highly variable. Two cases have been reported to remit spontaneously. Others have required a combination of plasmapheresis
and long term immunosuppression, although in one of these cases the patient died shortly after receiving Plasma Exchange (PE). Other fatalities without remission have been described by, amongst others, Morvan himself.
, 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.
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. Clinical features pertaining to insomnia include daytime drowiness 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. In a case documented in 1974, PSG findings documented the sustained absence of all sleep rhythms for up to a period of 4 months.
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.
(EMG) discloses spontaneous, repetitive motor unit
or single fiber discharges firing in irregular rhythmic bursts at high intraburst frequencies. Some of the muscles exhibiting twitching include the bilateral gastrocnemii
, quadriceps femoris, biceps brachii, and right masseter. In vivo
electrophysiological studies suggest at least some dysfunction of the muscle cell membrane
. In the examined muscles, no abnormal insertional activity or fibrillation
potentials were noted. Nerve conduction studies were normal.
, neuromytonia should be added to the list of differential diagnoses.
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. Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus
.
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 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. 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
. 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.
. Raised serum levels of antibodies to VGKCs have been reported in three patients with Morvan’s Syndrome. Binding of serum
from a patient with Morvan’s Syndrome to the hippocampus
in a similar pattern of antibodies to known VGKC suggest that these antibodies can also cause CNS dysfunction. Additional antibodies against neuromuscular junction
channels and receptors have also been described. Experimental evidence exists that these anti-VGKC antibodies cause nerve hyperexcitability by suppression of voltage gated K+ outward currents, whereas other, yet undefined humoral factors have been implicated in anti-VGKC antibody negative neuromyotonia.
It is believed that antibodies to the Shaker-type K+ channels (the Kv1 family) are the type of potassium channel most strongly associated with acquired neuromyotonia and Morvan’s Syndrome.
Whether VGKC antibodies play a pathogenic role in the encephalopathy
as they do in the peripheral nervous system
is as yet unclear. It has been suggested that the VGKC antibodies may cross the blood-brain barrier
and act centrally, binding predominantly to thalamic and striatal
neurons causing encephalopathic and autonomic features.
alone or in combination with steroids, sometimes also with thymectomy
and azathioprine
, have been the most frequently used therapeutic approach in treating Morvan’s Syndrome. However, this does not always work, as failed response to steroids and to subsequently added plasmapheresis have been reported. Intravenous immunoglobulin was effective in one case.
In one case, the dramatic response to high-dose oral prednisolone
together with pulse methylprednisolone
with almost complete disappearance of the symptoms within a short period should induce consideration of corticosteroids.
In another case, the subject was treated with haloperidol
(6 mg/day) with some improvement in the psychomotor agitation and hallucinations, but even high doses of carbamazepine
given to the subject failed to improve the spontaneous muscle activity. Plasma Exchange (PE) was initiated, and after the third such session, the itching, sweating, mental disturbances, and complex nocturnal behavior improved and these symptoms completely disappeared after the sixth session, with improvement in insomnia and reduced muscle twitching. However, one month after the sixth PE session, there was a progressive worsening of insomnia and diurnal drowsiness, which promptly disappeared after another two PE sessions.
In another case, the subject was treated with prednisolone (1 mg/kg body weight) with carbamazepine, propanolol, and andamitriptyline. After two weeks, improvement with decreased stiffness and spontaneous muscle activity and improved sleep was observed. After another 7–10 days, the abnormal sleep behavior disappeared completely.
In another case, symptomatic improvement with plasmapherisis, thymectomy, and chronic immunosuppression provide further support for an autoimmune or paraneoplastic basis.
Although thymectomy is believed to be a key element in the proposed treatment, there is a reported case of Morvan’s Syndrome presenting itself post-thymectomy.
Thymoma, prostate
adenoma, and in situ carcinoma
of the sigmoid colon
have also been found in patients with Morvan’s Syndrome.
(LE). These include the CNS symptoms consisting of insomnia, hallucinations, and disorientation, as well as dementia and psychosis. Both entities can be paraneoplastic and associated with thymoma
. Recently, VGKC antibodies were found in patients with LE, strengthening the hypothesis that LE and Morvan’s Syndrome may be closely connected. Varying symptoms may be used to determine which of the two diseases the subject has. Amnesia, seizures, and mesial temporal lobe
structural abnormalities are features of LE, whereas myokymia, hyperhydrosis, and insomnia favor Morvan’s Syndrome.
Augustin Marie Morvan
Augustin Marie Morvan was a French physician, politician, and writer. He is best-known for treating the first recorded case of the eponymous Morvan's syndrome, a rare neurological disorder marked by acute insomnia. Morvan served as a deputy to the French National Assembly that inaugurated the...
. “La chorée fibrillaire” was first coined by Morvan in 1890 when describing patients with multiple, irregular contractions
Muscle contraction
Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...
of the long muscles, cramping, weakness, pruritus, hyperhidrosis
Hyperhidrosis
Hyperhidrosis is the condition characterized by abnormally increased perspiration, in excess of that required for regulation of body temperature.-Classification:Hyperhidrosis can either be generalized or localized to specific parts of the body...
, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, and delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
.
It normally presents with a slow insidious onset over months to years.
Approximately 90% of cases spontaneously go into remission, while the other 10% of cases lead to death.
Overview
In 1890, Morvan described a patient with myokymiaMyokymia
Myokymia, is an involuntary, spontaneous, localized quivering of a few muscles bundles within a muscle, but which are insufficient to move a joint.One type is superior oblique myokymia....
(muscle twitching) associated with muscle pain, excessive sweating, and disordered sleep.
This rare disorder is characterized by severe insomnia, amounting to no less than complete lack of sleep (agrypnia) for weeks or months in a row, and associated with autonomic alterations consisting of profuse perspiration with characteristic skin Miliaria
Miliaria
Miliaria is a skin disease marked by small and itchy rashes. Miliaria is a common ailment in hot and humid conditions, such as in the tropics and during the summer season...
(miliaria rubra, sweat rash or prickly heat), tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, increased body temperature, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
. Patients display a remarkable hallucinatory behavior, and peculiar motor disturbances, which Morvan reported under the term “fibrillary chorea” but which are best described nowadays as neuromyotonic discharges.
The association of the disease with thymoma, tumour, autoimmune diseases, and autoantibodies suggests an autoimmune or paraneoplastic aetiology. Besides an immune-mediated etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
, it is also believed to occur in gold, mercury, or manganese poisoning.
Prevalence
There are only about 14 reported cases of Morvan’s Syndrome in the English Literature.With only a limited number of reported cases, the complete spectrum of the Central Nervous System
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) symptomatology has not been well established.
The natural history of Morvan’s is highly variable. Two cases have been reported to remit spontaneously. Others have required a combination of plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
and long term immunosuppression, although in one of these cases the patient died shortly after receiving Plasma Exchange (PE). Other fatalities without remission have been described by, amongst others, Morvan himself.
General 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 myoclonusMyoclonus
Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...
, slight muscle atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
in the limbs, absence of tendon reflexes in the lower limbs and diffuse erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
especially on the trunk with scratching lesions of the skin.
Insomnia
In all of the reported cases, the need for sleepSleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
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. Clinical features pertaining to insomnia include daytime drowiness 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
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
and connected limbic structures in the pathology indicate the prominent role that the limbic thalamus plays in the pathophysiology of sleep. In a case documented in 1974, PSG findings documented the sustained absence of all sleep rhythms for up to a period of 4 months.
Electroencephalography
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
(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.
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. ElectromyographyElectromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
(EMG) discloses spontaneous, repetitive motor unit
Motor unit
”A motor unit is a single α-motor neuron and all of the corresponding muscle fibers it innervates; all of these fibers will be of the same type . When a motor unit is activated, all of its fibers contract...
or single fiber discharges firing in irregular rhythmic bursts at high intraburst frequencies. Some of the muscles exhibiting twitching include the bilateral gastrocnemii
Gastrocnemius muscle
In humans, the gastrocnemius muscle is a very powerful superficial pennate muscle that is in the back part of the lower leg. It runs from its two heads just above the knee to the heel, and is involved in standing, walking, running and jumping. Along with the soleus muscle it forms the calf muscle...
, quadriceps femoris, biceps brachii, and right masseter. In vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
electrophysiological studies suggest at least some dysfunction of the muscle cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. In the examined muscles, no abnormal insertional activity or fibrillation
Fibrillation
Fibrillation is the rapid, irregular, and unsynchronized contraction of muscle fibers. An important occurrence is with regards to the heart.-Cardiology:There are two major classes of cardiac fibrillation: atrial fibrillation and ventricular fibrillation....
potentials were noted. Nerve conduction studies were normal.
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 laryngospasmLaryngospasm
In medicine, laryngospasm is an uncontrolled/involuntary muscular contraction of the laryngeal cords. The condition typically lasts less than 60 seconds, and causes a partial blocking of breathing in, while breathing out remains easier. It may be triggered when the vocal cords or the area of the...
, neuromytonia should be added to the list of differential diagnoses.
Studies have shown subtly decreased metabolism on positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) and single photon emission computed tomography
Single photon emission computed tomography
Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...
(SPECT) in the left inferior frontal and left temporal lobe
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
s. Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
.
Cerebral Spinal Fluid (CSF) shows normal protein, glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, white blood cell, and IgG index but there are weak oligoclonal bands, absent in the blood. Marked changes in circadian serum levels of neurohormones 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. 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
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
. 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.
Voltage Gated Potassium Channels
Antibodies against voltage-gated potassium channels (VGKC), which are detectable in about 40% of patients with acquired neuromytonia, have been implicated in Morvan’s pathophysiologyPathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
. Raised serum levels of antibodies to VGKCs have been reported in three patients with Morvan’s Syndrome. Binding of serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
from a patient with Morvan’s Syndrome to the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
in a similar pattern of antibodies to known VGKC suggest that these antibodies can also cause CNS dysfunction. Additional antibodies against neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
channels and receptors have also been described. Experimental evidence exists that these anti-VGKC antibodies cause nerve hyperexcitability by suppression of voltage gated K+ outward currents, whereas other, yet undefined humoral factors have been implicated in anti-VGKC antibody negative neuromyotonia.
It is believed that antibodies to the Shaker-type K+ channels (the Kv1 family) are the type of potassium channel most strongly associated with acquired neuromyotonia and Morvan’s Syndrome.
Whether VGKC antibodies play a pathogenic role in the encephalopathy
Encephalopathy
Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...
as they do in the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
is as yet unclear. It has been suggested that the VGKC antibodies may cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and act centrally, binding predominantly to thalamic and striatal
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
neurons causing encephalopathic and autonomic features.
Prospective Treatment
In most of the reported cases, the treatment options were very similar. PlasmapheresisPlasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
alone or in combination with steroids, sometimes also with thymectomy
Thymectomy
A thymectomy is an operation to remove the thymus. It usually results in remission of myasthenia gravis with the help of medication including steroids...
and azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, have been the most frequently used therapeutic approach in treating Morvan’s Syndrome. However, this does not always work, as failed response to steroids and to subsequently added plasmapheresis have been reported. Intravenous immunoglobulin was effective in one case.
In one case, the dramatic response to high-dose oral prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
together with pulse methylprednisolone
Methylprednisolone
Methylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....
with almost complete disappearance of the symptoms within a short period should induce consideration of corticosteroids.
In another case, the subject was treated with haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
(6 mg/day) with some improvement in the psychomotor agitation and hallucinations, but even high doses of carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
given to the subject failed to improve the spontaneous muscle activity. Plasma Exchange (PE) was initiated, and after the third such session, the itching, sweating, mental disturbances, and complex nocturnal behavior improved and these symptoms completely disappeared after the sixth session, with improvement in insomnia and reduced muscle twitching. However, one month after the sixth PE session, there was a progressive worsening of insomnia and diurnal drowsiness, which promptly disappeared after another two PE sessions.
In another case, the subject was treated with prednisolone (1 mg/kg body weight) with carbamazepine, propanolol, and andamitriptyline. After two weeks, improvement with decreased stiffness and spontaneous muscle activity and improved sleep was observed. After another 7–10 days, the abnormal sleep behavior disappeared completely.
In another case, symptomatic improvement with plasmapherisis, thymectomy, and chronic immunosuppression provide further support for an autoimmune or paraneoplastic basis.
Although thymectomy is believed to be a key element in the proposed treatment, there is a reported case of Morvan’s Syndrome presenting itself post-thymectomy.
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 collegen. How these two diseases relate to one another is still unclear.Thymoma, prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
adenoma, and in situ carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
of the sigmoid colon
Sigmoid colon
The sigmoid colon is the part of the large intestine that is closest to the rectum and anus. It forms a loop that averages about 40 cm...
have also been found in patients with Morvan’s Syndrome.
Similarity to Limbic Encephalitis
The symptoms of Morvan’s Syndrome have been noted to bear a striking similarity to limbic encephalitisLimbic encephalitis
Limbic encephalitis is a form of encephalitis.In a small number of cases, the pathogens responsible for encephalitis attack primarily the limbic system , often causing memory deficits similar to those observed in Alzheimer's disease or Creutzfeldt-Jakob disease Limbic encephalitis is a form of...
(LE). These include the CNS symptoms consisting of insomnia, hallucinations, and disorientation, as well as dementia and psychosis. Both entities can be paraneoplastic and associated with thymoma
Thymoma
Thymoma is a tumor originating from the epithelial cells of the thymus. Thymoma is an uncommon tumor, best known for its association with the neuromuscular disorder myasthenia gravis. Thymoma is found in 15% of patients with myasthenia gravis. Once diagnosed, thymomas may be removed surgically...
. Recently, VGKC antibodies were found in patients with LE, strengthening the hypothesis that LE and Morvan’s Syndrome may be closely connected. Varying symptoms may be used to determine which of the two diseases the subject has. Amnesia, seizures, and mesial temporal lobe
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
structural abnormalities are features of LE, whereas myokymia, hyperhydrosis, and insomnia favor Morvan’s Syndrome.