Weak magnetic fields as a novel therapeutic modality in Parkinson's disease.
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Biomedical subjects
Publications and source records attributed to R Sandyk.
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It is now well recognized that the hypothalamus is an important site of neuropathology in Parkinson's disease (PD). Lewy bodies, a marker of nerve cell degeneration and a pathological hallmark of PD, have been observed frequently in the hypothalamus of PD patients by Lewy (1923) and other investigators and confirmed by more recent systematic studies by Langston & Forno (1978). Both Lewy and Langston & Forno found a predilection of Lewy body formation in specific hypothalamic nuclei with the tuberomammillary, lateral, and posterior areas containing by far the highest average counts per nucleus. Selective vulnerability of the tuberomammillary, lateral, and posterior hypothalamic cell groups to degeneration has been observed also in aging, postencephalitic Parkinsonism, Alzheimer's disease, and schizophrenia. The susceptibility of these particular nuclei to degenerative changes including Lewy body formation is not presently understood nor are the mechanisms by which Lewy bodies are formed in PD and other CNS disorders. Accumulation of amines, a pathological process which follows degeneration of catecholamine-containing neurons in experimental animals, also occurs most frequently in the lateral and posterior hypothalamic areas. In the present communication we propose that in PD, amine accumulation may be a precursor to Lewy body formation and that the susceptibility of certain hypothalamic areas to Lewy body formation may be related to their propensity to accumulate amines. Furthermore, the frequent co-existence of Lewy bodies and Alzheimer's neurofibrillary tangles in the lateral and posterior hypothalamic nuclei suggest that they may share a common pathogenetic etiology. If confirmed, this hypothesis may provide an experimental model by which the formation of Lewy bodies and neurofibrillary tangles may be investigated.
We have previously demonstrated that magnetoencephalographic (MEG) brain measurements in patients with seizure disorders show significant MEG activity often in the absence of conventional EEG abnormalities. We localized foci of seizure activity using the mapping technique characterized by the ISO-Spectral Amplitude (ISO-SA) on the scalp distribution of specified spectral components or frequency bands of the emitted MEG Fourier power spectrum. In addition, using an electronic device, we utilized the above recorded activity to emit back the same intensity and frequency of magnetic field to the presumed epileptic foci. Using this method we were able, over the past two and one-half years, successfully to attenuate seizure activity in a cohort of over 150 patients with various forms of epilepsy. We present a patient with severe epilepsy and behavioral disturbances in whom application of an external artificial magnetic field of low intensity produced a substantial attenuation of seizure frequency which coincided with an improvement in the patient's behavior. This case demonstrates that artificial magnetic treatment may be a valuable adjunctive procedure in the management of epilepsy.
Application of external weak magnetic fields recently has been reported to be efficacious in the treatment of a 62-year-old patient with idiopathic Parkinson's disease (PD) complicated by levodopa-induced fluctuations in motor response ("on-off"). I report an additional case of a 67-year-old man with idiopathic PD and levodopa-related motor fluctuations who likewise experienced marked and sustained improvement in Parkinsonian symptoms and amelioration of "on-off" symptoms following the application of external weak magnetic fields. Based on these observations it is concluded that artificial weak magnetic fields may be beneficial for the treatment of PD complicated by levodopa-related "on-off" phenomenon. Furthermore, since in experimental animals external magnetic fields alter the secretion of melatonin, which in turn has been shown to regulate striatal and mesolimbic dopamine-mediated behaviors, it is proposed that the antiParkinsonian effects of weak magnetic fields are mediated via the pineal gland.
Investigations aimed at identifying the clinical characteristics that discriminate tardive dyskinesia (TD) from non-TD patients have yielded disparate findings. We have suggested, based on pharmacological and neuroradiological studies, that TD in schizophrenia may be a covariate of positive symptoms while drug-induced parkinsonism (DIP) may relate to negative symptoms. To investigate this hypothesis, we examined in 47 institutionalized schizophrenic patients the relationship of TD and DIP with psychopathology clusters rated on the Positive and Negative Syndrome Scale. We found that involuntary movements of TD were significantly associated with the activation cluster (p < .01), whereas DIP was significantly associated with the anergia cluster (p < .01). These findings thus support the position that TD is a specific facet of the positive syndrome in schizophrenia, while DIP is a specific feature of the negative syndrome. Clinically, the data suggest that schizophrenic patients with predominant positive symptoms may be at increased risk for TD, while those with prominent negative features could be at increased risk for DIP. In analogy with the positive/negative dichotomy, we propose that TD could be regarded as a "positive," while DIP as a "negative" movement disorder.
In a recent Editorial published in this Journal, I presented a new and revolutionary method for the treatment of Parkinson's disease (PD). I reported that extracranial treatment with picoTesla magnetic fields (MF) is a highly effective, safe, and revolutionary modality in the symptomatic management of PD. My conclusion was based on experience gained following the successful treatment of over 20 Parkinsonian patients, two of whom had levodopa-induced dyskinesias. None of the patients developed side effects during a several month period of follow-up. In the present communication, I present two reports. The first concerns four Parkinsonian patients in whom picoTesla MF produced a remarkable and sustained improvement in disability. Three of the patients had idiopathic PD and the fourth patient developed a Parkinsonian syndrome following an anoxic episode. In all patients, treatment with MF was applied as an adjunct to antiParkinsonian medication. The improvement noted in these patients attests to the efficacy of picoTesla MF as an additional, noninvasive modality in the therapy of the disease. The second report concerns two demented Parkinsonian patients in whom treatment with picoTesla MF rapidly reversed visuospatial impairment as demonstrated by the Clock Drawing Test. These findings demonstrate, for the first time, the efficacy of these MF in the amelioration of cognitive deficits in Parkinson's disease. Since Alzheimer's pathology frequently coexists with the dementia of Parkinsonism, these observations underscore the potential efficacy of picoTesla MF in the treatment of dementias of various etiologies.
The present communication concerns a 50 year-old woman with a 15 year history of chronic-progressive multiple sclerosis (MS) in whom extracranial application of picoTesla magnetic fields (MF) produced a dramatic and sustained improvement in disability. In contrast, administration of melatonin (3 mg, P.O.) produced in this patient a rapid exacerbation of disability which was reversed subsequently by treatment with MF. It is hypothesized that the therapeutic effects of picoTesla MF involve the mediation of the pineal gland which is known to act as a magnetosensor. The report demonstrates, for the first time, the remarkable efficacy of weak MF in the symptomatic treatment of chronic-progressive MS and underscores the pivotal role of the pineal gland in the pathophysiology of MS. If confirmed by a larger cohort of patients, extracranial application of picoTesla MF may prove as an extremely efficacious, nonpharmacological modality for the treatment of MS.
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Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.
In the following communication we discuss evidence suggesting that an abnormal opioid-gonadotrophin interaction at the midbrain may be essential to the clinical expression of vocal tics in Tourette's Syndrome (TS). Data derived from animal studies and the striking similarity between the symptomatology of TS and encephalitis lethargica (EL) add further support to our hypothesis implicating an abnormal opioid-gonadotrophin interaction in the pathophysiology of TS.
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Primary lumbosacral plexus neuropathy (LSPN) is a well-defined syndrome characterized by pain, weakness and atrophy in the distribution of the lumbosacral plexus. Previous reports of LSPN have stressed the benign nature of the syndrome. Patients generally have a nearly complete recovery in months to years following the initial event. Two patients presenting with a relapsing form of LSPN are reported. The diagnosis of LSPN was based on clinical and electromyographic features, and no underlying cause was found on initial evaluation or subsequent follow-up over a 6- to 8-year period. We suggest that these patients represent a clinically and possibly pathologically distinct subgroup of LSPN.
Despite current intensive research, the pathophysiology of tardive dyskinesia (TD), a serious neurological side effect of neuroleptic treatment, is poorly understood. Prompted by the observation of an increased incidence and severity of abnormal perioral movements in neuroleptic-treated pinealectomized, as compared to intact rats, we suggested that the pineal gland exerts a protective effect which mitigates against the development of TD and, by inference, that reduced melatonin secretion may be related to the pathophysiology of TD. To investigate this proposition further, we studied the association of TD with pineal calcification (PC) on CT scan in chronic schizophrenic patients. Our findings revealed a significant association between TD and PC and suggest, furthermore, that PC may be a neuroradiological marker of TD. Since PC may reflect diminished secretory activity of the gland, these findings support the hypothesis that the pathophysiology of TD is linked to disturbances of melatonin secretion. The clinical and therapeutic implications of these novel findings are discussed. In the following communication, in which we introduce the hypothesis that disturbances of 5-HT and melatonin secretion are related to the pathophysiology of TD. Subsequently, we present a series of studies which relate to the association of TD with PC. We conclude by presenting the hypothesis that disturbances in melatonin secretion may also be relevant to the pathophysiology of Tourette's syndrome.
Seasonal affective disorder is characterized by recurrent winter depression associated with hypersomnia, overeating, and carbohydrate craving. The severe form of winter depression affects about 5% of the general population and is believed to be caused by light deficiency. About 70%-80% of patients with winter depression experience attenuation of symptoms when exposed to bright light therapy. Hypotheses pertaining to the pathogenesis of winter depression implicate the effects of light on different characteristics of circadian rhythms. One of the environmental factors which may be implicated, in addition to light, in the pathophysiology of winter depression is the geomagnetic field. There is strong indication that the pineal gland is a magnetosensitive system and that changes in the ambient magnetic field alter melatonin secretion and synchronize the circadian rhythms. In man, shielding of the ambient magnetic field significantly desynchronizes circadian rhythms which could be gradually resynchronized after application of magnetic fields. The strength of the environmental magnetic field diminishes during the winter months, leading to increased susceptibility for desynchronization of circadian rhythms. Thus, since the acute application of magnetic fields in experimental animals resembles that of acute exposure to light with respect to melatonin secretion (i.e., suppression of melatonin secretion), magnetic treatment might be beneficial for patients with winter depression. In addition, since the environmental light and magnetic fields, which undergo diurnal and seasonal variations, influence the activity of the pineal gland, we propose that a synergistic effect of light and magnetic therapy in patients with winter depression would be more physiological and, therefore, superior to phototherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Disorganization of circadian rhythms, a hallmark of aging, may be related causally to the progressive deterioration of memory functions in senescence and possibly Alzheimer's disease (AD). In experimental animals, disruption of circadian rhythms produces retrograde amnesia by interfering with the circadian organization of memory processes. The circadian system is known to be synchronized to external 24 h periodicities of ambient light by a neural pathway extending from the retina to the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. There is also evidence that the earth's magnetic field is a time cue ("Zeitgeber") of circadian organization and that shielding of the ambient magnetic field leads to disorganization of the circadian rhythms in humans. Since aging is associated with a delay of the circadian rhythm phase, and since light, which phase advances circadian rhythms, mimics the effects of magnetic fields on melatonin secretion, we postulate that application of magnetic fields might improve memory functions in the elderly as a result of resynchronization of the circadian rhythms. Moreover, since the circadian rhythm organization is more severely disrupted in patients with AD, it is possible that magnetic treatment might prove useful also in improving memory functions in these patients. If successful, application of magnetic fields might open new avenues in the management of memory disturbances in the elderly and possibly in AD.
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Multiple sclerosis (MS) is a chronic demyelinating disease of unknown etiology. Clinical, neurochemical, and neuroradiological data implicate the pineal gland in the pathophysiology of MS. To investigate the relationship of MS to the pineal gland further, we surveyed the prevalence of pineal calcification (PC) on CT scan in a cohort of 29 MS patients (7 men, 22 women, mean age: 40.1 years, SD = 8.9) who were admitted consecutively to a neurological service for acute exacerbation of symptoms. For the purpose of comparison, we also surveyed the prevalence of choroid plexus calcification (CPC) in the sample. Twenty-one age and sex-matched neurological patients served as controls (5 men, 16 women, mean age: 37.0, SD = 9.2). PC was seen in 100% of MS patients, while 72.4% patients (N = 21) had CPC. In the control sample, PC was found in 42.8% (N = 9) and CPC in 28.5% (N = 6). Thus, the strikingly high prevalence of PC in MS provides indirect support for an association between MS and abnormalities of the pineal gland. Moreover, since pineal melatonin is involved in neuroimmunomodulation, we propose, for the first time, that abnormalities of pineal melatonin functions are implicated in the pathophysiology of the disease.