Pain-Related Vertex Evoked Potentials. Comparison of Surface Electrical to Heat Stimulation.

INTRODUCTION: Demonstration of nociceptive fiber abnormality is important for diagnosing neuropathic pain and small fiber neuropathies. This is usually assessed by brief heat pulses using lasers, contact heat, or special electrodes. We hypothesized that pain-related evoked potentials to conventional surface electrical stimulation (PREPse) can index Aδ afferences despite tactile Aß fibers coactivation. PREPse may be more readily used clinically than contact heat evoked potentials (CHEPS). METHODS: Twenty-eight healthy subjects. Vertex (Cz-A1/A2) recordings. Electrical stimulation of middle finger and second toe with conventional ring, and forearm/leg skin with cup, electrodes. Contact heat stimulation to forearm and leg. Compression ischemic nerve blockade. RESULTS: PREPse peripheral velocities were within the midrange of Aδ fibers. N1-P1 amplitude increased with pain numerical rating scale graded (0-10) electrical stimulation (n = 25) and decreased with increasing stimulation frequency. Amplitudes were unchanged by different presentation orders of four stimulation intensities. PREPse N1 (∼130 milliseconds) and N2 (∼345 milliseconds) peaks were approximately 40 milliseconds earlier than that with CHEPS. PREPse and CHEPS N1-N2 interpeak latency (∼207 milliseconds) were similar. PREPse became unrecordable with nerve blockade of Aδ fibers. CONCLUSIONS: PREPse earlier N1 and N2 peaks, and similar interpeak N1-N2 latencies and central conduction velocities, or synaptic delays, to CHEPS are consistent with direct stimulation of Aδ fibers. The relation of vertex PREPse amplitude and pain, or the differential effects of frequency stimulation, is similar to pain-related evoked potential to laser, special electrodes, or contact heat stimulation. The relationship to Aδ was validated by conduction velocity and nerve block. Clinical utility of PREPse compared with CHEPS needs validation in somatosensory pathways lesions.

Navigating migraine care through the COVID-19 pandemic: an update.

The worldwide treatment gap for migraine before COVID-19 inevitably widens as attention focuses on an international emergency. Migraine hits people particularly in their early and middle years, potentially reduces quality of life and productivity, and remains a common emergency presentation. This article examines the impact of COVID-19 on migraine, and changing aspects of migraine care during and after the pandemic. Many risk factors for severe COVID-19-older age, male gender, cardiac and respiratory diseases, diabetes, obesity, and immunosuppression-are less frequent in migraineurs. Telemedicine is effective for migraine follow-up, and needs ongoing evaluation. Most migraine treatments can start or continue in acute COVID-19, with care to avoid drug interactions. Close contact procedures (botulinum toxin, acupuncture and steroid injections) are avoided in lockdown or in the vulnerable. Secondary effects of COVID-19, including long COVID and its economic impact, are probably equal or greater in people with migraine. Migraine and other long-term conditions need adequate resourcing to prevent personal, social and economic suffering. Treating migraine, a sequel of COVID, potentially reduces the impact of long COVID.

Spinal cord infarction with ipsilateral segmental neuropathic pain and flaccid paralysis. A functional role for human afferent ventral root small sensory fibres.

This paper illustrates the cases of two patients with an acute onset of right brachial neuropathic pain, flaccid paralysis and contralateral thermal and thermal pain hypoesthesia, without posterior column impairment nor pyramidal signs below the segmental lesion. MRI showed right sided spinal cord infarction, in the anterior spinal artery territory between C1 and C5 in one patient and between C3 and C7 in the other. Contact Heat Evoked Potentials and Quantitative Thermal Sensory testing are consistent with contralateral, but not ipsilateral, spinothalamic tract involvement. Electromyographic results established ipsilateral segmental denervation and somatosensory evoked responses were consistent with dorsal column sparing. Unilateral anterior cervical spinal cord infarction may present with acute ipsilateral segmental neuropathic pain, lower motor neurone-type weakness, contralateral thermoanalgesia and no pyramidal signs. The ipsilateral pain provides novel evidence that in some instances, ventral roots can play a role in nociception in humans. The infarcted territory may result from occlusion of a sulcal commissural artery or a number of more proximal vessels (including a single or duplicated anterior spinal artery, vertebral arteries or feeding radicular arteries).

Familial limb pain and migraine: 8-year follow-up of four generations.

Background Migraine limb pain may be under-recognized in adults and children. There is little information about familial forms of this disorder. Objectives To describe the clinical and inheritance patterns of familial migraine limb pain over four generations and to review the evidence for limb pain as a manifestation of migraine. Methods Prospective clinical and pedigree analysis with an 8-year follow-up of 27 family members. Results Eight members of the family had benign recurrent limb pain associated with headache in a dominant inheritance pattern. Limb pain occurred before, during or after the headache, with probable or definite migraine with aura, migraine without aura and lower-half headache. The limb pain fulfilled the International Headache Society criteria for aura in six patients and also occurred without headache in three. Four members of the family had recurrent abdominal pain and/or motion sickness in childhood. Conclusions This is the first report of dominant familial limb pain temporally associated with migraine headache, starting in adulthood or starting in childhood and continuing into adulthood. A search for a genetic marker is indicated. Limb pain should be included as a childhood periodic syndrome linked to migraine and recognized as part of the migraine spectrum in adults.

Syncope and Raynaud's disease.

OBJECTIVE: To investigate an association between syncope and Raynaud's disease (RD), its clinical features, and the effect of treatment with nifedipine. DESIGN: One-year prospective study of new outpatients after 3 initial clinical observations. SETTING: Neurology clinics at Chelsea and Westminster, Royal Free, Barnet, and Edgware Hospitals. PATIENTS: Ten women and 1 man. The group had a mean (SD) age of 33 (17) years. Mean (SD) follow-up was 24 (36) months. INTERVENTION: Treatment with nifedipine. OUTCOME MEASURES: Observed vs expected frequency of syncope in RD, temporal relation between syncope and Raynaud's phenomenon, clinical features, and response to nifedipine treatment. RESULTS: Eight additional patients with syncope and RD were identified from 603 new patients (1.3%); we had expected only 1 patient to be identified with syncope and RD (P=.003). A chance association between RD and migraine with recurrent syncope was unlikely (P=.01). The prevalence of RD in patients with syncope with migraine was higher than expected (P=.03), but that of migraine in patients with RD was not (P=.2). All 11 patients had 5 or more syncopal episodes for a median of 2 years (range, 0.1-62 years). Three patients had previous diagnoses of nonepileptic attacks. Syncope was preceded by or contemporaneous with Raynaud's phenomenon in 10 patients (P=.02). Nine patients had migraine; headache was contemporaneous with syncope in 4 patients as expected by chance (P=1.0). In all patients, syncope was preceded by brainstem or vertebrobasilar symptoms, and it ceased after treatment with nifedipine. Raynaud's disease and migraine improved less. CONCLUSIONS: The association of syncope to RD was unrelated to chance or migraine. The temporal relation between syncope and Raynaud's phenomenon but not headache was statistically significant. Treatment with nifedipine stopped recurrent syncope in all patients. Syncope related to RD may result from brainstem ischemia. Unexplained recurrent syncope should prompt screening for RD.

SCA3 presenting as an isolated axonal polyneuropathy.

OBJECTIVES: To highlight an unexpected clinical presentation and to review the associated polyneuropathy phenotypes of SCA3. DESIGN: Clinical follow-up. SETTING: Neurological referral center. PATIENT: Middle-aged man with no family history for SCA3. RESULTS: Presentation with an isolated axonal, distal, symmetric, sensorimotor polyneuropathy for 6 years before developing a cerebellar syndrome prompting genetic testing for SCA3. CONCLUSION: SCA3 can present with an isolated axonal, distal, symmetric, sensorimotor polyneuropathy.

Dysarthria in amyotrophic lateral sclerosis: A review.

Dysarthria is a motor disorder of speech characterized by abnormalities of the articulation and intelligibility of speech. Phonation and the rate of facial movements may also be affected. Understanding the nature and course of dysarthria in amyotrophic lateral sclerosis (ALS) is important because loss of communication prevents patients from participating in many activities, may lead to social isolation, and reduces the quality of life. The goal of management of dysarthria in ALS patients is to optimize communication effectiveness for as long as possible. The information about dysarthria in ALS is dispersed in physiological, pathological, speech therapy, otorhinolaringological and neurological publications. This review summarizes the current state of knowledge on the clinical features, differential diagnosis, pathophysiology, investigations and management of dysarthria in ALS patients. There is a need to compare the different methods used to assess dysarthria and for controlled clinical trials to assess therapeutic strategies.

Amyotrophic lateral sclerosis and ocular flutter.

A previously unreported association of amyotrophic lateral sclerosis and ocular flutter is presented. It is hypothesized that initial loss of brainstem inhibitory interneurons resulted in disinhibition of burst interneurons and that the ocular flutter subsequently disappeared as burst interneurons also became affected by the disease process. The association adds clinical evidence of involvement of brainstem interneurons to other evidence of involvement of neurons other than motor neurons in the disease process.

Nineteen-year follow-up of Waldenström's-associated neuropathy and Bing-Neel syndrome.

We describe the follow-up of a patient with Waldenström's macroglobulinemia who developed mild predominantly sensory peripheral neuropathy, Bing-Neel syndrome, and, after 17 years, acute mononeuropathy multiplex associated with increasing paraprotein levels. Nerve biopsy demonstrated deposition of IgM in the endoneurium and perineurium. Magnetic resonance imaging showed extension of the cerebral white-matter abnormality. We suggest that the pathogenetic mechanism of the mononeuropathy multiplex may include direct IgM deposition. Late peripheral nerve complications appeared to be related to the paraprotein level.

Widespread loss of neuronal populations in the spinal ventral horn in sporadic motor neuron disease. A morphometric study.

The cytopathology and loss of neurons was studied in 7670 neurons from the ventral horn of the third lumbar segment of the spinal cord of six sporadic motor neuron disease (MND) patients compared with 7568 neurons in seven age matched control subjects. A modified Tomlinson et al. [Tomlinson BE, Irving D, Rebeiz JJ. Total numbers of limb motor neurones in the human lumbosacral cord and an analysis of the accuracy of various sampling procedures. J Neurol Sci 1973;20:313-27] sampling procedure was used for neuronal counts. The ventral horn was divided in quadrants. Neuronal populations were also classified by the maximum cell diameter through the nucleolus. There was widespread loss of neurons in all quadrants of the ventral horn in MND. Size distribution histograms showed similar neuron loss across all populations of neurons. The dorsomedial quadrant contains almost exclusively interneurons and the ventrolateral quadrant mostly motor neurons. The cytopathology of neurons in the dorsomedial quadrant and of large motorneurons in the ventrolateral quadrant MND was similar. In the dorsomedial quadrant, neuron loss (56.7%) was similar to the loss of large motor neurons in the ventrolateral quadrant (64.4%). The loss of presumed motor neurons and interneurons increased with increased disease duration. There was no evidence that loss of presumed interneurons occurred prior, or subsequent, to loss of motor neurons. We conclude that, in sporadic MND, all neuronal populations in the ventral horn are affected and that interneurons are involved to a similar extent and in parallel with motor neurons, as reported in the G86R transgenic mouse model of familial MND. The increasing evidence of loss of neurons other than motor neurons in MND suggests the need for revising the concept of selective motor neuron vulnerability.

Limitations of inferences from observational databases in amyotrophic lateral sclerosis: all that glitters is not gold.

Data from three observational databases have suggested that survival in patients with ALS who take riluzole is far greater than that reported in randomized controlled studies. This editorial discusses why therapeutic efficacy cannot be inferred from observational databases. Data in these databases cannot control for biases in treatment assignment or for differences in intensity of follow-up or supportive care. The retrospective riluzole data, as presented so far, have not demonstrated comparability between the treated and untreated groups across all known prognostic factors, including vital capacity at the start of the observation period. Furthermore, the similarity of untreated patients to historical cohorts likely reflects adverse selection. Optimization of analysis in retrospective studies may be accomplished by allowing full access to data to all interested parties.