Reuven Sandyk

Nocturnal Plasma Melatonin and Alpha-Melanocyte Stimulating Hormone Levels During Exacerbation of Multiple Sclerosis

The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS). To investigate this hypothesis further, we studied nocturnal plasma melatonin levels and the presence or absence of pineal calcification (PC) on CT scan in a cohort of 25 patients (5 men, 20 women; mean age: 41.1 years; SD = 11.1; range: 27-72) who were admitted to a hospital Neurology service for exacerbation of symptoms. Plasma alpha-melanocyte stimulating hormone (alpha-MSH) estimations were included in the study since there is evidence for a feedback inhibition between alpha-MSH and melatonin secretion. Abnormal melatonin levels were found in 13 patients (52.0%), 11 of whom had nocturnal levels which were below the daytime values (i.e., < 25 pg/ml). Although melatonin levels were unrelated to the patients age and sex, there was a positive correlation with age of onset of symptoms (p < .0001) and an inverse correlation with the duration of illness (p < .05). PC was noted in 24 of 25 patients (96%) underscoring the pathogenetic relationship between MS and the pineal gland. Alpha-MSH levels were undetectable in 15 patients (60.0%), low in two patients (8.0%), normal in seven patients (28.0%), and elevated in one patient (4.0%). Collectively, abnormal alpha-MSH levels were found in over 70% of patients. These findings support the hypothesis that MS may be associated with pineal failure and suggest, furthermore, that alterations in the secretion of alpha-MSH also occur during exacerbation of symptoms. The relevance of these findings to the pathogenesis of MS are discussed.

Nocturnal Melatonin Secretion in Multiple Sclerosis Patients with Affective Disorders

The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS), a chronic demyelinating disease of CNS. Since nocturnal melatonin secretion is low in some groups of patients with mental depression, we predicted lower melatonin secretion in MS patients with history of affective illness compared to those without psychiatric disorders. To test this hypothesis, we studied single nocturnal plasma melatonin levels and the incidence of pineal calcification (PC) on CT scan in a cohort of 25 MS patients (4 men, 21 women; mean age = 39.4 years, SD = 9.3), 15 of whom had a history of coexisting psychiatric disorders with predominant affective symptomatology. Other factors that may be related to depression such as vitamin B12, folic acid, zinc, magnesium, and homocysteine, were also included in the analysis. Neither any of the metabolic factors surveyed nor the incidence of PC distinguished the psychiatric from the control group. However, the mean melatonin level in the psychiatric patients was significantly lower than in the control group. Since low melatonin secretion in patients with depression may be related to a phase-advance of the circadian oscillator regulating the offset of melatonin secretion, we propose that the depression of MS likewise may reflect the presence of dampened circadian oscillators. Furthermore, since exacerbation of motor symptoms in MS patients may be temporally related to worsening of depression, we propose that circadian phase lability may also underlie the relapsing-remitting course of the disease. Consequently, pharmacological agents such as lithium or bright light therapy, which have been shown to phase-delay circadian rhythms, might be effective in the treatment of affective symptoms in MS as well as preventing motor exacerbation and hastening a remission from an acute attack.

Resolution of longstanding symptoms of multiple sclerosis by application of picotesla range magnetic fields

Recent clinical reports have suggested that treatment with extremely weak magnetic fields (MF) in the picoTesla range is an efficacious modality for the symptomatic therapy in patients with multiple sclerosis (MS) during the remission and exacerbation periods of the disease. The present communication concerns a 64 year old woman with a 22 year history of MS of the chronic-progressive type who presented with a longstanding history of ataxia of gait, weakness in the legs, difficulties with swallowing, loss of bladder control, blurred vision, diplopia, chronic fatigue, and cognitive impairment. In this patient two 30 minute treatments with MF on two separate days resulted in a dramatic improvement of symptoms. Specifically, the patient experienced marked improvement in balance and gait as well as increased strength in the legs to the extent that she was able to abandon the use of a walker within 48 hours after initiation of magnetic treatment. In addition, there was complete resolution of diplopia, bladder dysfunction, and fatigue with improvement in mood and cognitive functions. The report attests to the unique efficacy of extremely weak MF in the symptomatic treatment of patients with MS including those patients with a chronic progressive course of the disease and supports the hypothesis that dysfunction of synaptic conductivity due to neurotransmitter deficiency specifically of serotonin rather than demyelination underlies the neurologic deficits of the disease.

Magnetic fields normalize visual evoked potentials and brainstem auditory evoked potentials in multiple sclerosis.

The present communication concerns a 46 year old woman with a 10 year history of chronic progressive multiple sclerosis (MS) in whom external application of magnetic fields (MF) (7.5 picoTesla; 5 Hz) during a period of remission resulted in a rapid and dramatic improvement in symptoms including vision, cerebellar symptomatology (ataxia and dysarthria), mood, sleep, bowel and bladder functions as well as fatigue. Improvement in the patients symptoms was associated with normalization of the pretreatment latencies of the visual evoked potentials and brainstem auditory evoked potential responses within a week after initiation of magnetic treatment. This report demonstrates that treatment with picoTesla MF is an effective, nonpharmacological modality in the management of MS and for the first time documents reversal of abnormal evoked potential responses by this treatment. The pineal gland is a magnetosensor. As MF affect the release of the pineal glands principal hormone, melatonin, it is hypothesized that the effects of picoTesla MF in MS are partly mediated by the pineal gland which has recently been implicated in the pathogenesis of MS (Sandyk, 1992 a; b).

Successful treatment of an acute exacerbation of multiple sclerosis by external magnetic fields.

A 55 year old woman with multiple sclerosis presented with a 5 week history of an exacerbation of symptoms. Prominent among these symptoms was trigeminal neuralgia, migraine headaches, blurring of vision, and ataxia of gait. While treatment with carbamazepine (TegretolR) (800 mg/d) and oral prednisolone (15 mg/d) over a 4 week period produced no improvement in symptoms, externally applied magnetic fields (MF) (7.5 picoTesla; 5 Hz) placed over the scalp for a 7 minute period on three different days resulted in a complete resolution of symptoms within two weeks of initiation of treatment. Partial relief of the neuralgic pain and headaches was obtained immediately after completion of the first treatment indicating that resolution of symptoms was related to the effects of MF and not to a spontaneous remission. This is the first report demonstrating the clinical efficacy of pico Tesla range MF in rapidly resolving an acute relapse of MS.

The Co-Occurrence of Multiple Sclerosis and Migraine Headache: The Serotoninergic Link

The occurrence of migraine headaches in patients with multiple sclerosis (MS) has been recognized for quite some time but the significance of this association to the pathogenesis of MS largely has been ignored. Several reports have documented that migraine headaches may occur during exacerbation of symptoms and may even herald the onset of relapse in MS. We present three MS patients in whom migraine headaches developed during a period of relapse. As migraine has been linked to changes in serotonin (5-HT) functions, the emergence of migraine headaches coincident with the onset of relapse implicates dysregulation of the 5-HT system in the pathophysiology of MS. This hypothesis is plausible considering the evidence that MS patients are serotonergically depleted and that 5-HT is involved in maintaining the integrity of the blood brain barrier, disruption of which is believed to occur in the initial stages of exacerbation of MS symptoms. Furthermore, this hypothesis may have potential therapeutic implications in the treatment of exacerbations of MS and possibly in the prevention of relapse in the disease.

Vitamin B12 and its relationship to age of onset of multiple sclerosis

Attention has been focused recently on the association between vitamin B12 metabolism and the pathogenesis of multiple sclerosis (MS). Several recent reports have documented vitamin B12 deficiency in patients with MS. The etiology of this deficiency in MS is unknown. The majority of these patients do not have pernicious anemia and serum levels of the vitamin are unrelated to the course or chronicity of the disease. Moreover, vitamin B12 does not reverse the associated macrocytic anemia nor are the neurological deficits of MS improved following supplementation with vitamin B12. It has been suggested that vitamin B12 deficiency may render the patient more vulnerable to the putative viral and/or immunologic mechanisms widely suspected in MS. In the present communication, we report that serum vitamin B12 levels in MS patients are related to the age of onset of the disease. Specifically, we found in 45 MS patients that vitamin B12 levels were significantly lower in those who experienced the onset of first neurological symptoms prior to age 18 years (N = 10) compared to patients in whom the disease first manifested after age 18 (N = 35). In contrast, serum folate levels were unrelated to age of onset of the disease. As vitamin B12 levels were statistically unrelated to chronicity of illness, these findings suggest a specific association between the timing of onset of first neurological symptoms of MS and vitamin B12 metabolism. In addition, since vitamin B12 is required for the formation of myelin and for immune mechanisms, we propose that its deficiency in MS is of critical pathogenetic significance.

Treatment with AC pulsed electromagnetic fields improves olfactory function in Parkinson's disease

Olfactory dysfunction is a common symptom of Parkinsons disease (PD). It may manifest in the early stages of the disease and infrequently may even antedate the onset of motor symptoms. The cause of olfactory dysfunction in PD remains unknown. Pathological changes characteristic of PD (i.e., Lewy bodies) have been demonstrated in the olfactory bulb which contains a large population of dopaminergic neurons involved in olfactory information processing. Since dopaminergic drugs do not affect olfactory threshold in PD patients, it has been suggested that olfactory dysfunction in these patients is not dependent on dopamine deficiency. I present two fully medicated Parkinsonian patients with long standing history of olfactory dysfunction in whom recovery of smell occurred during therapeutic transcranial application of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density. In both patients improvement of smell during administration of EMFs occurred in conjunction with recurrent episodes of yawning. The temporal association between recovery of smell and yawning behavior is remarkable since yawning is mediated by activation of a subpopulation of striatal and limbic postsynaptic dopamine D2 receptors induced by increased synaptic dopamine release. A high density of dopamine D2 receptors is present in the olfactory bulb and tract. Degeneration of olfactory dopaminergic neurons may lead to upregulation (i.e., supersensitivity) of postsynaptic dopamine D2 receptors. Presumably, small amounts of dopamine released into the synapses of the olfactory bulb during magnetic stimulation may cause activation of these supersensitive receptors resulting in enhanced sense of smell. Interestingly, in both patients enhancement of smell perception occurred only during administration of EMFs of 7 Hz frequency implying that the release of dopamine and activation of dopamine D2 receptors in the olfactory bulb was partly frequency dependent. In fact, weak magnetic fields have been found to cause interaction with biological systems only within narrow frequency ranges (i.e., frequency windows) and the existence of such frequency ranges has been explained on the basis of the cyclotron resonance model.

Estrogen's impact on cognitive functions in multiple sclerosis.

It has long been suspected that hormonal factors contribute directly and indirectly to the etiology and pathogenesis of multiple sclerosis (MS). The susceptibility of MS is higher in women than in men and women are even more susceptible to hormonal influences when onset occurs at an early or delayed age. Pregnancy has a short-term favorable effect on the course of the disease but there is an increased rate of relapse during the post-partum period. In addition, women often report premenstrual exacerbation of their symptoms with remission during menses. These findings suggest that in women estrogens may exert a stabilizing effect on the clinical manifestations of MS. The role of estrogens is supported also by observations of a higher incidence of cognitive impairment in women than men with MS. A 50 year old woman with a remitting progressive MS experienced profound deterioration in cognitive functions during withdrawal from estrogen therapy which was initiated for the treatment of amenorrhea. Improvement in cognitive functions occurred shortly after she restarted therapy with an estrogen/progesterone preparation and was maintained during long term therapy. Serotonin (5-HT) mechanisms have been implicated in memory functions and estrogens modulate these functions through an interaction with 5-HT2 receptors in the cerebral cortex and limbic system. It is suggested that estrogen withdrawal induces impairment in cognitive functions through dysregulation of 5-HT2 receptor activity and 5-HT neurotransmission. These findings suggest that estrogens have a beneficial influence on cognitive functions in MS patients and that hormonal supplementation might be advised in menopausal and postmenopausal MS patients for the prevention of cognitive deterioration.

Resolution of Lhermitte's Sign in Multiple Sclerosis by Treatment with weak Electromagnetic Fields

Lhermittes sign, the occurrence of an electrical sensation passing down the back to the legs on flexion of the neck is a common and characteristic feature of multiple sclerosis (MS) which is related to spinal cord lesions affecting the posterior columns and cervical nerve roots. The Lhermittes sign, which has been reported to occur at some time in up to 25% of MS patients, is seldom painful but is often a cause of distress to the patient and usually a marker of increased disease activity. Treatment with extracranial picotesla range pulsed electromagnetic fields (EMFs) has been found efficacious in the management of various MS symptoms including pain syndromes. The present communication concerns three MS patients in whom two brief applications of EMFs resulted in resolution of the Lhermittes sign which emerged during a period of exacerbation of symptoms in one patient and during a prolonged phase of symptom deterioration in the other two patients. As the cause of the Lhermittes sign is thought to result from the spread of ectopic excitation in demyelinated plaques in the cervical and thoracic regions of the spinal cord, it is hypothesized that the effects of EMFs are related to the reduction of axonal excitability via a mechanism involving changes in ionic membrane permeability. A systemic effect on pain control systems is also postulated to occur secondary to the effects of EMFs on neurotransmitter activity and pineal melatonin functions. This report underscores the efficacy of picotesla EMFs in the management of paroxysmal pain symptoms in MS.