The pathophysiology of sexual dysfunction in Parkinson's disease: An overview.

Sexual dysfunction is a common, poorly recognized, poorly discussed (often because of cultural perceptions and sensitivities), bothersome and neglected aspect of the range of non-motor symptoms of Parkinson's disease (PD). The spectrum of sexual dysfunction in PD ranges from hyposexuality-based disturbances to hypersexuality-dominated behaviors in the context of drug-induced impulse control disorder. The pathophysiological mechanisms underlying PD-related sexual dysfunction, specifically for hyposexual disorders, are thus heterogeneous and still not fully understood. However, central and peripheral neural mechanisms secondary to the hallmark pathological alterations of the disease (alpha-synuclein deposition and nigrostriatal degeneration) and to the associated network and neurotransmitter dysfunctions, together with the effects of dopaminergic therapies, seem to play an important role in the development of sexual disturbances. In this chapter, we therefore review the neuroanatomical and neurophysiological basis of sexual function in humans, and we provide insights on the pathophysiological mechanisms of hyposexuality and hypersexuality in PD.

The Story of Levodopa: A Long and Arduous Journey.

Levodopa (L-dopa) is the gold standard in the management of Parkinson's disease (PD). It dates back to 1500 to 1000 BC when it was used in the Indian Ayurvedic and Chinese system of medicine. Certain beans such as velvet beans and broad beans contain L-dopa. The plant Mucuna pruriens (Mp) or velvet bean, cultivated in Eastern India and Southern China, contains L-dopa at a concentration of 5% and was used for the management of PD. Later, workers have documented the neuroprotective, neurorestorative, and immunomodulatory properties of Mp. Double-blind studies conducted in the Western world have proved the efficacy of Mp and reported some toxic side effects as well. In the Western world, the credit for isolating L-dopa from the seeds of Vicia faba or broad bean goes to Markus Guggenheim, a biochemist from Sweden in 1913. However, it has been used with success ever since Arvid Carlsson established the reversibility of reserpine-induced akinesia in rabbits in the late 1950s with the use of intravenous dopamine, and Oleh Hornykiewicz demonstrated its deficiency in the striatum in 1960-1961. George Cotzias used it in patients in a low and slow incremental fashion in 1967, and Melvin Yahr and his colleagues performed double-blind study on in-patients with success in 1969. Complications with its long-term use, particularly the on-off phenomenon, and dyskinesias appeared soon, and measures have been undertaken to reduce their incidence. Researches on alternative modes of delivery are carried out in various centers, and others are under investigation in the laboratories.

Frontal assessment battery in Parkinson's disease: A study on 170 patients.

BACKGROUND: Frontal assessment battery (FAB) was devised as a specific study design to assess frontal lobe dysfunction. Since Parkinson's disease (PD) is often associated with cognitive and other higher mental function complications, FAB test has been carried out by a number of workers to assess the integrity of the frontal lobe. On the other hand, the other frequently conducted test, performed in order to evaluate the mental status, is the Mini Mental State examination of Folstein (MMSE), but its reliability has been questioned in PD, since it does not assess the functions of the frontal lobe alone. MATERIAL AND METHODS: The present study was undertaken in order to assess the suitability of application of the FAB test in Indian patients and to perform its comparative analysis with the MMSE scale. RESULTS AND CONCLUSIONS: It was observed that the FAB test correlated with the age and the level of education of the patient. The results also correlated with that of the MMSE study, in spite of the fact that the latter is not considered to be a test which can assess exclusively the status of the frontal lobe. To the best of our knowledge, this is first study undertaken in India in this regard.

Edgar Adrian and Patrick Merton: Names Blurred with the Passage of Time.

Edgar Douglas Adrian and Patrick Anthony Merton are two supreme neurophysiologists from England in the last century whose names are almost forgotten these days. Adrian's work on all-or-none phenomenon in nerve and muscle excitability ushered in a new era and Merton's servo theory of muscular movement and muscle fatigue added a new dimension to the understanding of stretch reflex and deep tendon reflexes. Both of them trained and worked at Trinity College, Cambridge and both were elected as Fellow of the Royal Society and Adrian in addition, was awarded the Nobel Prize in 1932 along with Charles Scott Sherrington.

Walter Edward Dandy (1886-1946): The epitome of adroitness and dexterity in Neurosurgery.

Walter Edward Dandy did pioneering work in Neurosurgery in the early part of the 19th century. He worked all his life at the Johns Hopkins Hospital in USA and contributed extensively to research in hydrocephalus, the physiology of the cerebrospinal fluid and devised the technique of pneumoencephalography, apart from performing the first clipping operation in cerebral aneurysm and the division of the trigeminal nerve in neuralgic pain. This article summarizes his immense contributions in the field of Neurosurgery.

Johann Bernhard Aloys von Gudden and the Mad King of Bavaria.

Bernhard von Gudden was a psychiatrist in Prussia and he was summoned in March 1886 to examine King Ludwig II for his apparently insane activities like, profligate spending and erratic behaviour. A team of four estimable psychiatrists pronounced that he was not capable ruling. Consequently, he was dethroned and kept in a castle under supervision of von Gudden. Gudden championed the idea of 'no restraint' and advocated free movement of insane persons and one evening in June, he accompanied the King during an evening stroll to a lake. A few hours later, the corpus of both of them were recovered under mysterious circumstances. Autopsy suggested that the King was drowned but no post-mortem examination was performed on von Gudden. There are plenty of controversies regarding their death like, murder, accidental death or even natural death from cardiac arrest following immersion in cold water, but no incontrovertible conclusion could be arrived at, even after scrupulous analysis by historians and even the diagnosis of insanity of the King has been doubted. Some even suggested that the opinion of psychiatrists were sought as a pretense in order to depose the King.

James Wenceslaus Papez, His Circuit, and Emotion.

James Papez worked on the anatomical substrates of emotion and described a circuit, mainly composed of the hippocampus, thalamus and cingulum, and published his observations in 1937. However, such an idea existed before him, as evidenced by the rudimentary indications from Paul Broca, and Paul MacLean added some other structures like, septum, amygdala, and hypothalamus in its ambit and called it the limbic system. Paul Ivan Yakovlev, proposed a circuit which also referred to orbitofrontal, insular, anterior temporal lobe, and other nuclei of thalamus. Further works hinted at cerebellar projections into this system and the clinical picture of aggression, arousal and positive feeding responses with stimulation of cerebellar nuclei, attests its possible role. Finally, the work of Heinrich Klüver and Paul Bucy of the United States of America on ablating the temporal lobes and amygdala and the resultant behaviour of the animals, almost incontrovertibly adduced evidence for the operation of a neural circuitry in the genesis of emotion. Additionally, Papez circuit may also be concerned with memory and damage to its various components in Parkinson's disease, Alzheimer's disease, Korsakoff's syndrome, semantic dementia, and global amnesia, where cognitive disturbance is almost universal, lends credence to its putative role.

Sexual Dysfunctions in Parkinson's Disease: An Underrated Problem in a Much Discussed Disorder.

Sexual dysfunctions (SDs) are one of the most neglected nonmotor symptoms in Parkinson's disease (PD). A number of reasons including social and cultural factors might explain, at least partially, why SD is still one of the most underrecognized aspects of the condition after 200 years since the very first description by James Parkinson. SD has not been extensively investigated, however, a number of studies have shown a high prevalence of decreased libido, orgasmic dysfunction in both men and women with PD, and erectile dysfunction in male subjects. Moreover, SD in PD also comprises the increasingly recognized hypersexuality that is often associated with PD treatment. Taken together, SD in PD includes a remarkable range of symptoms and conditions that often require a multidisciplinary approach regarding assessment, investigation, and treatment.

Frederic Andrews Gibbs and the Assassination of John Fitzgerald Kennedy.

Frederic Gibbs, the peerless expert on electroencephalogrphy was summoned to provide opinion on the EEG tracing of Jack Ruby, who murdered Lee Harvey Oswald, the assassin of John Fitzgerald Kennedy, the American President, in 1963. Gibbs pleaded that the tracing suggested features indicative of psychomotor epilepsy and Ruby killed Oswald in a state of fugue. His view was not agreed upon but Gibbs stood his ground unflinchingly. Subsequent appeals to the higher court spared Ruby from imminent execution and finally he died a natural death from metastatic complications of carcinoma of the lung in 1967.

Hallmarks of Clinical Aspects of Parkinson's Disease Through Centuries.

James Parkinson published a treatise "An Essay on The Shaking Palsy" in 1817. However, there is historical evidence that there were rudimentary descriptions of the disease long before Parkinson brought it to light. Later day physicians have added to the spectrum of the motor aspects of the disease over the last 200 years and the gamut of its clinical presentation is now known to be more ubiquitous than what was supposed earlier. In the 1960s, atypical Parkinsonism is identified as a distinct and separate entity, and after the introduction of levodopa in clinical practice, a variety of late motor complications have been described. Various stages of disability and motor scales have been devised which have helped in identifying and classifying the degree of severity of the disease. However, such impeccable was the original description that virtually little could be modified and later works have only added to the original text.

1892 and the tribulations of Joseph Babinski.

In the early 1880s, Joseph Babinski was appointed as Chef de Clinique under Jean-Martin Charcot at Salpétrière, Paris, in France. He appeared for the post of Professeur Agrégé, the pinnacle of academic distinction in France in 1892. Charles Bouchard, the earliest pupil of Charcot, who described the Charcot-Bouchard aneurysm along with his master, was the Chief of the Board of Jury. Charcot and Bouchard did not see eye to eye in the later period, and when German Sée, an external examiner did not join the board of examiners following illness, Bouchard, instead of seeking the assistance of an alternate examiner, employed the special right of Vote of Absence. Babinski and all other pupils of Charcot were unsuccessful, while those of Bouchard, came out with flying colors. An embittered Babinski, along with some of the other unsuccessful candidates, appeared before the Ministry of Public Assistance after a protracted legal battle for nearly 2 years but lost the case. They were even ordered by the court to pay on behalf of the the successful candidates for the legal battle. Babinski never sat for the examination again and this is the story of one of the most ignominious episodes in an examination anywhere.

The stretch reflex and the contributions of C David Marsden.

The stretch reflex or myotatic reflex refers to the contraction of a muscle in response to its passive stretching by increasing its contractility as long as the stretch is within physiological limits. For ages, it was thought that the stretch reflex was of short latency and it was synonymous with the tendon reflex, subserving the same spinal reflex arc. However, disparities in the status of the two reflexes in certain clinical situations led Marsden and his collaborators to carry out a series of experiments that helped to establish that the two reflexes had different pathways. That the two reflexes are dissociated has been proved by the fact that the stretch reflex and the tendon reflex, elicited by stimulation of the same muscle, have different latencies, that of the stretch reflex being considerably longer. They hypothesized that the stretch reflex had a transcortical course before it reached the spinal motor neurons for final firing. Additionally, the phenomenon of stimulus-sensitive cortical myoclonus lent further evidence to the presence of the transcortical loop where the EEG correlate preceded the EMG discharge. This concept has been worked out by later neurologists in great detail, and the general consensus is that indeed, the stretch reflex is endowed with a conspicuous transcortical component.

Deep tendon reflex: The background story of a simple technique.

Wilhelm Erb and Carl Otto Westphal from Prussia first described the knee jerk in the same issue of the journal Archiv für Psychiatrie und Nervenkrankheiten in January 1875. This article retraces the history of development of 'deep tendon reflex' as an integral clinical sign during every neurological examination. The history of the evolving shapes of the reflex hammer, the iconic trademark and the ultimate signature of a neuroscientist, is also presented.

Godfrey Newbold Hounsfield (1919-2004): The man who revolutionized neuroimaging.

Godfrey Hounsfield, a biomedical engineer contributed enormously towards the diagnosis of neurological and other disorders by virtue of his invention of the computed axial tomography scan for which he was awarded the Nobel Prize in 1979. Working for the Electrical and Musical Industry (EMI) Limited and in collaboration with two radiologists, James Ambrose and Louis Kreel, he introduced the use of this machine in 1971 at the Atkinson Morley's Hospital in Wimbledon. He continued to improve the quality of the devise and the human head was scanned for the first time in 1972. He continued his work on imaging of the human body was later concentrated on the next step in diagnostic radiology namely, magnetic resonance imaging.

Spinocerebellar ataxia type 6 in eastern India: Some new observations.

INTRODUCTION: Spinocerebellar ataxias (SCAs) are hereditary, autosomal dominant progressive neurodegenerative disorders showing clinical and genetic heterogeneity. They are usually manifested clinically in the third to fifth decade of life although there is a wide variability in the age of onset. More than 36 different types of SCAs have been reported so far and about half of them are caused by pathological expansion of the trinucleotide, Cytosine Alanine Guanine (CAG) repeat. The global prevalence of SCA is 0.3-2 per 100,000 population, SCA3 being the commonest variety worldwide, accounting for 20-50 per cent of all cases, though SCA 2 is generally considered as the commonest one in India. However, SCA6 has not been addressed adequately from India though it is common in the eastern Asian countries like, Japan, Korea and Thailand. OBJECTIVE: The present study was undertaken to identify the prevalence of SCA6 in the city of Kolkata and the eastern part of India. MATERIALS AND METHODS: 83 consecutive patients were recruited for the study of possible SCAs and their clinical features and genotype were investigated. RESULTS: 6 of the 83 subjects turned out positive for SCA6, constituting therefore, 13.33% of the patient pool. DISCUSSION: SCA6 is prevalent in the eastern part of India, though not as frequent as the other common varieties. CONCLUSIONS: Further community based studies are required in order to understand the magnitude of SCA6 in the eastern part, as well as in other regions of India.

Sporadic and familial myoclonic dystonia: Report of three cases and review of literature.

Myoclonic dystonia refers to a clinical syndrome characterized by rapid jerky movements along with dystonic posturing of the limbs. Clinically, it is characterized by sudden, brief, electric shock-like movements, mostly involving the upper extremities, shoulders, neck and trunk. Characteristically, the movements wane with consumption of small dose of alcohol in about 50% of cases. Additionally, dystonic contractions are observed in most of the patients in the affected body parts and some patients may exhibit cervical dystonia or graphospasm as well. It may manifest as an autosomal dominant condition or sometimes, as a sporadic entity, though there are doubts whether these represent cases with reduced penetrance. The condition is usually treated with a combination of an anticholinergic agent like, benztropine, pimozide and tetrabenazine. We report one sporadic case and one familial case where the father and the son are affected. The cases were collected from the Movement Disorders Clinic of Bangur Institute of Neurosciences, Kolkata, West Bengal in a period of ten months. Myoclonic dystonia is a rare condition and to the best of our knowledge, this series is the first one reported from our country. Videos of the patients are also provided with the article.

Cognitive impairment in idiopathic Parkinson's disease.

BACKGROUND: Cognitive symptoms are common in advanced Parkinson's disease (PD). However, assessment of cognitive impairment is difficult in PD because of accompanying motor symptoms and the coexistence of nonmotor symptoms. Specific subdomains affected in the disease are not reflected in the conventional scales used for assessing cognition. OBJECTIVES: This study was aimed at looking at the spectrum of cognitive impairment in the various phenotypes and stages of PD and the correlation of cognitive impairment with motor and nonmotor symptoms of PD. PATIENTS AND METHODS: Fifty PD patients fulfilling the UK PD Society Brain Bank's criteria were selected after obtaining explicit consent. Patients were assessed clinically and by using various scales like Scales for Outcomes in PD-Cognition (SCOPA-COG), mini-mental state examination, and Beck's Depression Inventory and Scoring. RESULTS: The mean age was 58 years, 82% of the patients were male, and the mean modified Hoehn and Yahr staging was 2. The most commonly affected domains were memory and executive functioning. Cognitive impairment was more in those with late-onset disease, more advanced stage of disease, and in the postural instability and gait disorder (PIGD) subgroup. The cognitive function deteriorated with increasing age and duration of the illness. Significant correlation with cognitive impairment was obtained for the manifestations of increased motor disability, presence of coexistent psychotic symptoms and depression. CONCLUSIONS: Cognitive impairment was common among PD patients, and it was more prevalent with increasing duration of the disease, in older patients, in late-onset disease, and in the PIGD subgroup. Increasing motor disability and associated psychotic symptoms as well as depression significantly increased the cognitive impairment.