Parkinson's Disease: Autonomic Symptoms

Parkinson's Disease with its four cardinal symptoms of tremor, rigidity, bradykinesia, and postural instability is becoming increasingly associated with dysautonomia. In fact, "autonomic complaints such as constipation may predae the motor signs of PD." Also, these nonmotor symptoms of PD are associated with significant decrease in quality of life. To date, no tested therapies are available to treat these autonomic symptoms.

Shannon KM. Dopamine: So "last century". Neurology 2007;69:329-332.

Basal Ganglia Circuits

The concepts of the direct pathway and indirect pathway take up a day of medical school neuroscience courses. They usually follow a discussion of the four dopamine pathways: the nigrostriatal, mesocortical, mesolimbic, and tuberoinfundibular.

These circuits were recently featured in the journal Neurology.

Benarroch E. Endocannabinoids in basal ganglia circuits. Neurology 2007;69:306-309.

In the diagram featured in that article the only variation in the above schematic is the contribution of the substantia nigra pars compacta. According to the article, "dopaminergic inputs from the SNc modulate the activity of these pathways, exerting a net excitatory effect on the direct and a net inhibitory effect on the indirect pathway."

Dr. Benarrach says it better than I could: in the direct pathway "striatal neurons elicit a phasic inhibition of the GPi/SNr, leading to disinhibition of the thalamus and brainstem motor areas". The indirect pathway is explained thus: "since the GPe tonically inhibits the STN, activation of the indirect pathway disinhibits the STN. The resulting increase in STN activity leads to an increase in inhibitory output from the GPi/SNr, resulting in inhibition or termination of motor programs."

Justice Roberts has a Seizure

On July 31, 2007, the New York Times published an article of contradictory opinions in regards to the Chief Justice's July 30 seizure.

Early in the article his epilepsy is characterized as idiopathic while nearer to the end of the article one quoted physician calls it cryptogenic. There is obvious disagreement about whether he should receive antiepileptics.

The Chief Justice by definition has epilepsy, probably cryptogenic localization related epilepsy. On July 30 he had a seizure and as epileptics do, he returned to normal afterward. His evaluation, as I am sure he had 14 years ago, should include an MRI and an EEG. Contrary to the Times article, a CT scan does not offer much to his work-up. Both of these tests can be done as an outpatient. As the article states the MRI will probably be normal but it should be done anyway to rule out any intracranial pathology (tumor, stroke, etc.). An EEG can provide some guidance in this situation. If it is normal, then withholding treatment for now would be prudent. If it shows focal slowing or spikes with a normal MRI, then he likely has an underlying abnormality that cannot be found. With an abnormal EEG, the decision would have to be made whether to treat with an antiepileptic drug or wait. With two seizures in 14 years and the specter of medication side effects (including cognitive), hopefully Justice Roberts and his doctors decide to forgo treatment and wait.

Aphasia

Hillis AE. Aphasia: Progress in the last quarter of a century. Neurology 2007;69: 200-213.

This review article surveys the advances in the field, the value of current research, and what has been learned. Aphasia has grown much more complex than that of the Wernicke's and Broca's types. The paper is careful, that is, it is painstakingly nuanced. There are no broad sweeping proclamations. Localization is approximate. Our understanding of aphasia and, moreover, the localization of language, has grown exceedingly complex. Although in medical school, the Wernicke/Broca, receptive/motor, and fluent/dysfluent divide is stressed, the understanding of aphasia is far beyond these easy categories. Without diving in to deeply, a few of the more concrete points are delivered below.

Broca's aphasia, broadly includes "reduced phrase length, impaired melody and articulatory agility, diminished words per minute, and agrammatic sentence production". The different permutations and number of these independent yet intertwined deficits all arise from compromise of blood flow through the superior division of the left middle cerebral artery. The posterior, inferior frontal gyrus is implicated in deficit studies. Aphasias in the Wernicke's spectrum are associated with disruption of blood flow to the inferior division of the left MCA, which supplies the posterior, superior temporal gyrus.

Transcortical aphasias are characterized by intact repitition. Transcortical motor aphasia shares features of Broca's aphasia but with impaired repetition. Associated lesions occur "just anterior or superior to Broca's area, often caused by occlusion of the ACA or "watershed" areas between the ACA and the MCA." Conversely, transcortical sensory aphasia is caused by "lesions surrounding Wernicke's area, in the watershed territories between the MCA and PCA or the PCA territory. Mixed transcortical aphasia is global aphasia with preserved repetition. This syndrome shows dysfunctional cortex surrounding Broca's and Wernicke's areas, "sometimes known as 'isolation of the speech area'".

Conduction aphasia is characterized by phonemic paraphasias.

Pure alexia is usually caused by two lesions, one to the left occipital cortex caused by compromise of the left PCA, and the other to the splenium of the corpus callosum. The splenium lesion disrupts nerve tracts carrying visual information from the right occipital cortex to the left hemisphere language areas. These same two lesions can effect optic aphasia, in which an object cannot be identified by sight but can be identified through tactile cues.

The latter part of the article distinguishes different aphasias by their disrupted cognitive processes. Anecdotal examples of patients with selective aphasias demonstrate the separation of different cognitive functions, and at the same time, their overlap. Consult the article for this to be explained better than I could at this point.

Musicophilia

In the July 23, 2007 New Yorker, Oliver Sacks presents the tale of an orthopedic surgeon who demonstrated musicophilia and musicality after being struck by lightning. "A Bolt from the Blue" uses the case of the surgeon to dive into a discussion of the neural basis for out of body experiences and the sudden onset of artistic endeavors.

The article gives evidence for two hypotheses regarding how the unexpected emergence of musical ability may occur. The first involves strengthening of connections between perceptual systems in the temporal lobe and the limbic system. This is achieved by repetitive epileptic activity arising from a temporal focus. The emergence of hypermusia, a gain of function, intuitively seems to fit a hypothesis in which some neural connections, responsible for a certain function, are differentially strengthened. Conversely, and thus counterintuitively, loss of brain tissue, in this article by resection and stroke, has been associated with gain of musical ability. It is the disinhibition of abilities always present but not consciously engaged that is believed to cause this.

When a student taking a jazz class notes that he cannot appreciate rhythm after a temporal lobectomy, the loss of brain tissue mirrors a loss in ability. It is the gain of function after neurologic damage that runs counter to reason, and is therefore far more interesting.

In the past I discussed the case of a woman who became pain-free after a seizure.

Post-Hypoxic Movement Disorders

A healthy young male was struck by lightning in the front yard of his home. He developed ventricular fibrillation and was eventually resuscitated. An unclear period of anoxia produced ischemic lesions (DWI - positive) in his basal ganglia bilaterally. He spent an extended period of time in an acute care hospital. Neurology was reinvolved in his care three months after his initial presentation for full body jerks (myoclonus), rigidity, and a persistently open mouth with tongue dyskinesia. These three symptoms had all worsened after his valium was decreased by 50%. His physical exam reveal flexor posturing of the upper extremities with increased tone to the point of rigidity throughout. His hypoxic-ischemic injury has left him without the ability to speak or follow commands. He is able to track consistently with his eyes and move his neck and head toward a stimulus.

This patient's severe disability and seeming movement disorders led to the following paper. Some aspects of it are presented below.

Venkatesan A, Frucht S. Movement Disorders after Resuscitation from Cardiac Arrest. Neurol Clin 24 (2006) 123-132.

After hypoxic-ischemic injury, parkinsonism, dystonia, chorea, tics, athetosis, tremor, and myoclonus have all been described. Post-hypoxic myoclonus (PHM), which can be seen acutely or as a long-term sequela, may be focal, multifocal, or generalized. Acute PHM is characterized by severe, generalized myoclonic jerks in deeply comatose patients. The prognosis associated with acute PHM is extremely poor. The best evidence points to diffuse cortical damage as the cause. Treatment usually consists of IV sedation. Chronic PHM (Lance-Adams Syndrome) is characterized by action myoclonus involving the limbs, stimulus sensitivity, and negative myoclonic jerks. Localization is both cortical and subcortical.

"It seems that cortical myoclonus is much more common in chronic PHM than subcortical myoclonus, the latter of which tends to cause violent jerks of the proximal limbs and trunk."

First-line treatments are Clonazepam, valproate, and piracetam. Baclofen, diazepam, ethanol, methysergide, GHB, and levetiracetam have also been used.

Of greater importance to this case are the movement disorders caused by damage to the basal ganglia. There seems to be a spectrum of post-hypoxic dystonic and akinetic-rigid syndromes. The akinetic-rigid syndrome developing within three months of the hypoxic event is characterized by "bradykinesia, micrographia, axial and appendicular rigidity, resting or postural tremor, and marked postural instability." Treatment responses are dismal. Those with a dystonic syndrome areyounger than those with a more akinetic-rigid syndrome. Case series suggest that dystonic syndromes predominate in those with putaminal lesions, while the akinetic syndrome occurs in those with pallidal lesions. The mechanism of preferential damage to the basal ganglia has fallen into two camps: the vascular hypothesis which states that there is selective hypoperfusion to the basal ganglia during a hypoxic event; and the metabolic hypothesis which postulates that high metabolic requirements result in selective hypoxic damage.

"Regardless of the mechanism, it seems that damage to the basal ganglia with preservation of the pyramidal system is a pathologic correlate of delayed posthypoxic dystonia or akinetic-rigid syndromes."

Mobius Syndrome

Those with Mobius Syndrome are recognized by their facial diplegia. They lack any facial expression; they have difficulty eating and cannot fully close their eyes. In addition to paresis of CN VII bilaterally, they classically have CN VI pareses. CN V and VIII dysfunction and variable orofacial and limb malformations are also associated with the syndrome.

Since facial diplegia leads to social stigmatization, a surgery has been to developed to correct it. Performed in Toronto at the Hospital for Sick Children, it involves borrowing nerve from the masseter and muscle from the thigh. With practice, according to the website, patients "learn" to involuntarily smile. This has even happened in adults, testament to the plasticity of the human brain at all ages.

The syndrome was identified by the German neurologist Paul Julius Möbius. He should not be confused with August Ferdinand Möbius who independently described the Mobius strip or band. Mobius Band is also a rock group from Brooklyn.