Paroxysmal symptoms as the first manifestations of multiple sclerosis.

Twomey, J A; Espir, Michael

doi:10.1136/jnnp.43.4.296

Cited by 100 publications

(51 citation statements)

References 29 publications

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“…In particular, MS often produces confounding symptoms that can present intermittently, resolving and returning in a way that is decoupled from myelination status and include asymptomatic partial demyelination (clinicoradiographic dissociation; refs. [8][9][10][11][12].…”

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confidence: 99%

“…Indeed, partially demyelinated axons can recover the ability to conduct through a centimeter or more of demyelination in the optic nerve (13). The diverse clinical symptoms described above could result from axonal excitability changes causing conduction slowing or failure, stimulus-dependent afterdischarge (AD), and spontaneous spiking (9)(10)(11). An open question is whether these axonal excitability changes and their associated clinical manifestations reflect a single, common pathogenic process or whether each type of symptom (e.g., negative vs. positive, tonic vs. paroxysmal, etc.)…”

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confidence: 99%

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Imbalance of ionic conductances contributes to diverse symptoms of demyelination

Coggan

Prescott

Bartol

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Fast axonal conduction of action potentials in mammals relies on myelin insulation. Demyelination can cause slowed, blocked, desynchronized, or paradoxically excessive spiking that underlies the symptoms observed in demyelination diseases. The diversity and timing of such symptoms are poorly understood, often intermittent, and uncorrelated with disease progress. We modeled the effects of demyelination (and secondary remodeling) on intrinsic axonal excitability using Hodgkin-Huxley and reduced Morris-Lecar models. Simulations and analysis suggested a simple explanation for the breadth of symptoms and revealed that the ratio of sodium to leak conductance, g Na /g L , acted as a four-way switch controlling excitability patterns that included spike failure, single spike transmission, afterdischarge, and spontaneous spiking. Failure occurred when this ratio fell below a threshold value. Afterdischarge occurred at g Na /g L just below the threshold for spontaneous spiking and required a slow inward current that allowed for two stable attractor states, one corresponding to quiescence and the other to repetitive spiking. A neuron prone to afterdischarge could function normally unless it was switched to its "pathological" attractor state; thus, although the underlying pathology may develop slowly by continuous changes in membrane conductances, a discontinuous change in axonal excitability can occur and lead to paroxysmal symptoms. We conclude that tonic and paroxysmal positive symptoms as well as negative symptoms may be a consequence of varying degrees of imbalance between g Na and g L after demyelination. The KCNK family of g L potassium channels may be an important target for new drugs to treat the symptoms of demyelination. O ligodendrocytes and Schwann cells tightly wrap axons at regular intervals to form the myelin sheath that allows for rapid axonal conduction. Neuropathies involving axonal demyelination are characterized by the unraveling of this insulation and can affect both the central nervous system, as in the case of multiple sclerosis (MS), and the peripheral nervous system, as in Guillain-Barré syndrome.Causes of demyelination include immunologic disease processes, as well as lesions such as traumatic nerve damage, nonpenetrating spinal cord injuries, and chronic nerve compression (1-4). Regardless of the precise etiology, clinical presentation often involves negative (loss-of-function) symptoms, including loss of motor control (i.e., paresis) and sensory deficits such as blindness and numbness, as well as positive (gain-of-function) symptoms, including muscle spasms, tactile allodynia, and chronic pain that is constant or paroxysmal (1, 4-7). Which muscles or sensory modalities are affected depends on where in the nervous system the demyelinating lesions develop, but changes in conduction velocity alone are clearly insufficient to explain the breadth of symptoms observed, especially the positive ones. In particular, MS often produces confounding symptoms that can present intermittently, resolving and retu...

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confidence: 99%

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confidence: 99%

Imbalance of ionic conductances contributes to diverse symptoms of demyelination

Coggan

Prescott

Bartol

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Neither Parker nor his paper was mentioned in the article by Andermann et al However, because of the attention the article by Andermann et al received and the new interest in paroxysmal attacks in MS that the article by Andermann et al generated, Parker's 1946 article became more widely known and cited. 2,[4][5][6][7]15 In an article by Ostermann and Westerberg 7 published in 1975 on paroxysmal attacks in MS, Parker and Dr. Gustav Störring were both credited with the earliest descriptions of paroxysmal dysarthria and ataxia. In 1940, Störring published "Epilepsie und multiple Sklerose."…”

Section: Resultsmentioning

confidence: 99%

“…By 1980, paroxysmal dysarthria and ataxia was a wellrecognized phenomenon in MS and there were a total of 47 cases described in the literature. 15 However, there have been relatively few recent articles. With the advent of MRI, many of the modern articles have focused on identifying the location of the lesion responsible for causing paroxysmal dysarthria and ataxia.…”

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confidence: 99%

Harry Lee Parker and paroxysmal dysarthria and ataxia

et al. 2013

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Objective: To review descriptions of paroxysmal dysarthria and ataxia in multiple sclerosis (MS), with special attention given to Parker and his 1946 case series.Methods: Evaluation of original publications describing paroxysmal dysarthria and ataxia, bibliographic information, writings, and unpublished letters from the Mayo Clinic Historical Unit.Results: In 1940, Störring described a patient with MS with paroxysmal symptoms that included dizziness and trouble speaking, but also unilateral extremity weakness. In 1946, Parker published a series of 11 patients with paroxysmal dysarthria and ataxia. Six of these patients had MS, and he recognized this phenomenon as a manifestation of the disease. The term "paroxysmal dysarthria and ataxia" was first used in 1959 by Andermann and colleagues. Since that time, paroxysmal dysarthria and ataxia has become a well-recognized phenomenon in MS. More recent reports have suggested that the responsible lesion is located in the midbrain, near or involving the red nucleus. Paroxysmal motor and sensory phenomena are well-described complications of multiple sclerosis (MS). These stereotyped events are of sudden onset and brief duration, and can occur multiple times an hour. Paroxysmal symptoms that have been reported include diplopia, trigeminal neuralgia, facial paresthesia, pain, itching, tonic seizures, akinesia, and dysarthria and ataxia. [1][2][3] There is disagreement about who first described paroxysmal dysarthria and ataxia in MS, with some authors giving priority to Gustav Störring and others to Harry Lee Parker. Conclusions:2,4-7 Parker (figure) described patients with attacks of dysarthria and ataxia in 1946. Since then, paroxysmal dysarthria and ataxia has become a well-known phenomenon in MS, appearing in numerous neurology and MS textbooks. 1,2OBJECTIVE The objective of the study was to review the earliest descriptions of paroxysmal dysarthria and ataxia and its association with MS. Particular attention was given to Parker and his 1946 case series. The authors compared these early descriptions to subsequent case reports.METHODS The authors evaluated original publications describing paroxysmal dysarthria and ataxia in patients with MS, as well as bibliographic information, writings, and unpublished letters from the Mayo Clinic Historical Unit pertaining to Harry Lee Parker. The Harry Lee Parker Collection in the Mayo Clinic Historical Unit contains a quarter foot of material. PubMed was searched using the search term "paroxysmal dysarthria and ataxia" to identify more recent case reports and case series.

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“…Paroxysmal non-epileptic symptoms seem to respond to many different drugs, but only a few well controlled studies have been conducted. Twomey and Espir published a study that suggests the use of carbamazepine in the treatment of paroxysmal symptoms of multiple sclerosis (16). Other antiepileptic drugs, such as valproic acid and phenytoin have also shown success (17).…”

Section: Discussionmentioning

confidence: 99%