December 26, 2007

The Angular Gyrus

Located in the parietal lobe, near the superior edge of the temporal lobe, the angular gyrus is involved in the association of language and visual recognition. As noted in one paper, "posterior lesions, particularly of the angular gyrus, can produce quite pronouced anomia for visually recognised objects, and may be associated with alexia."

It occupies Brodmann area 39.

Kipps CM, Hodges JR. Cognitive Assessment for Clinicians. J Neurol Neurosurg Psychiatry 2005;76(Suppl 1):i22-i30.

November 29, 2007

Bell's Palsy

A large randomized, controlled, double-blinded trial published in the NEJM has concluded that Acyclovir and prednisolone dual therapy does not offer benefit over prednisolone alone. The jury is still out regarding the addition of valacyclovir. Severe cases respond best to valacyclovir and prednisolone dual therapy according to the published papers on the subject. For now prednisolone is certainly indicated for cases of Bell's palsy. Valacyclovir therapy may or may not add benefit. Not prescribing Valacyclovir would certainly be reasonable practice.

NEJM 2007;357:598-607

September 26, 2007

Restless Legs Syndrome

Two new papers outline the existence of three genes that can account for 70% of RLS. This runs counter to one commonly held perception of the condition: that it has a non-organic origin.

The function of the identified genes seem to be involved generally in the development of spinal cord sensory pathways and lower extremity development. This seems to correlate wiell with the symptomatology of RLS and its counterpart Periodic Leg Movements of Sleep.

Winkelmann J, Meitinger T, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nature Genet 2007;39:1000-1006


Another article of Oliver Sack's recently appeared in the September 24, 2007 New Yorker. In the form of an example driven narrative, it relays the story of Clive Wearing, a musician and musicologist, who became amnestic following a bout of encephalitis which damaged his medial temporal lobes and then some. The article doesn't clearly delineate the areas involved. His life after the illnes has been documented in a documentary and memoir by his wife.

His amnesia is characterized as the inability to form new memories as well as to remember parts of his past. He lives persistently in the present. There is no past and thereby an isolated present. His journal records this disconcerting reality as he repeatedly writes such statements as "I am conscious" and "This time I am properly awake," only to contradict himself a line later. This example of his condition is one of the more striking relayed in the article.

Clive's life, on the edge of the abyss or in the abyss, the metaphor used in the article which lends it its title, reveals how important memory is to making us fully human and conscious.

The idea of joking disease or Witzelsucht was presented in the article. This results from damage to the frontal lobes.

August 25, 2007

Transient Global Amnesia

TGA, once observed, is a remarkable condition. Its sufferers (for lack of a better word) lose the ability to form memories for up to 24 hours. They are marked by their propensity to repeat the same questions over and over again. They recover with only loss of memory for the discrete period of time in which they were impaired. The neuroimaging case cited below records bilateral hippocampal lesions that corresponded to the period of impairment. This included hyperintensity on FLAIR, restricted diffusion, and a SPECT scan showing hypoperfusion of bilateral hippocampi. Not all cases are associated with MRI changes but these studies seem to support the idea that hypoperfusion of the hippocampi without infarct causes the syndrome.

Di Filippo M, Calabresi P. Ischemic bilateral hippocampal dysfunction during transient global amnesia. Neurology 69;5:493.

Musical Automatisms

A few cases were collected together to see if ictal humming or singing had an anatomic correlate. Ictal singing seemed to correlate with right prefrontal seizures. Humming arose from temporal seizures. Singing seems to lateralize more to the right including "the superior temporal gyrus, the inferior central operculum, and particularly the inferior frontal gyrus."

Bartolomei F, et al. Clinical and Anatomic Characteristics of Humming and Singing in Partial Seizures. Neurology 69;5:490-2.

August 10, 2007


This is an effective medication for trigeminal neuralgia (for which it was originally approved) and partial and generalized seizures. It has the characteristic of possibly worsening absence and myoclonic seizures.

A well-known, dangerous, but rare complication is a drug rash which can progress to Stevens-Johnson Syndrome. In its most fulminant form, it can be fatal. This side effect can occur anytime during its administration. Toxic hepatitis and leukopenia may also occur. Since carbamazepine has other uses, it may be chosen despite its side effects, with the idea that it is treating more than just seizures.

Carbamazepine is also a medication in which levels can be checked. This can be helpful when a patient taking the drug presents with somnolence, dysarthria, and ataxia, and in addition on exam has fine nystagmus and asterixis. This presentation corresponded to a level of 20 (normal 8-12). How the level became this high is unknown.

August 4, 2007

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.

August 3, 2007

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."

August 1, 2007

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.


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.

July 25, 2007


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.

July 24, 2007

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."

July 18, 2007

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.

July 16, 2007

Meralgia Paresthetica

A muscular construction worker presented with low back pain and lateral left leg pain and numbness. Initially the physicians operated under the assumption the pain was caused by a kidney stone and he was admitted to the medicine service. After his renal CT and lumbar spine MRI were negative, but his pain persisted, neurology was consulted. On exam he had no weakness when full effort was given. His reflexes were normal. His only positive finding was an area of sensation loss consistent with the lateral femoral cutaneous nerve. A pelvic MRI was negative for a compressive lesion. Additional history revealed that he regularly wears a tool belt and he was exerting himself when the pain began. Clinically his syndrome was most consistent with meralgia paresthetica. It is caused by compression injury of the lateral femoral cutaneous nerve, usually as it passes under the inguinal ligament. Treatment includes NSAIDs, rest, and addressing the cause, e.g. obesity, posture, or tool belt. A local anesthetic nerve block can have diagnostic value, but the pain consultants for this patient balked. He was sent home with some improvement in pain and control with oral agents.

Erbay Hakan. Meralgia Paresthetica in Differential Diagnosis of Low-Back Pain. The Clinical Journal of Pain. 18:132-135.

July 12, 2007

Williams Syndrome

In the July 8 New York Times Sunday Magazine, David Dobbs reviews aspects of Williams Syndrome in "The Gregarious Brain". As others have done, he uses Williams syndrome as a springboard to discuss the genetics of personality, neuroscience, and even the evolution of language.

Williams Syndrome brains are on average 15% smaller than normal. A disproportionate amount of this discrepancy is accounted for by smaller dorsal regions. Ventral regions are denser in synaptic connections. Their affability has in part been linked to their lack of connection between the orbitofrontal cortices and amygdylae when interpreting menacing faces. Therefore they know no social fear.

The link between language and sociability, which Williams seems to demonstrate, provides support for the social-brain theory. It states that human neocortex increased to deal with larger social groups. Across primate species the size of the neocortex correlates with the size of the social group. In this theory language was a neocortical adaptation that allowed the maintenance of a large social network without physical grooming; instead relationships could be cultivated with verbal grooming.

July 7, 2007

fMRI as Lie Detector

Margaret Talbot takes on fMRI and the history of lie detection in her article "Duped" in the July 2, 2007 New Yorker. One company is touting fMRI as a way to exonerate the innocent and damn the guilty. The number of problems with this modality are numerous. One of the major problems is that sociopaths and hardened criminals have brains that respond to lying differently than normals, i.e. they lack pathways that reinforce remorse and guilt.

July 1, 2007

Intelligent Design

Not one to pass up flogging a scourge, Richard Dawkins takes on Michael Behe's new book The Edge of Evolution in the New York Times Book Review today. In the review, Dawkins defends science instead of proclaiming atheism or attacking religion. It seems that this is the best way to defend evolution and discount intelligent design: ask where's the evidence and where's the consensus? Dawkins rightly points out that Behe's stand has created a lucrative niche for himself on the speaking circuit. His books have surely found an audience.

June 25, 2007

Klippel-Feil Anomaly

This condition is a concern to neurologists because the anomaly, congenital fusion of cervical vertebrae, can sometimes have neurologic consequences. The vertebrae aren't actually fused; they fail to segment normally between the third and eighth weeks of development. On examination these patients have short necks, low hairlines, and limitation of neck movement. A recent example had one shoulder lower than the other. The picture in Bradley and Daroff (from where all information is borrowed and adapted) seems to demonstrate the same. Imaging reveals the fused vertebrae. Compression of nerve roots, cervical spinal cord, or vertebral or spinal artery can occur. Interestingly, suspected incomplete decussation of corticospinal fibers can cause mirror movements in children. There are many associated abnormalities, including bifurcated spinal cord. Many patients do just fine. The patient I saw had two discrete transient events characterized as right hand, lower arm, neck and face tingling. Neuroanatomically these events were difficult to ascribe to his K-F anomaly. DWI was negative. There was no history suggestive of an epileptic or migrainous phenomenon.

June 18, 2007


The author of This Is Your Brain on Music is perfectly poised to write a book about the neuroscience of music. Daniel J Levitin began his career as a musician and sound engineer, and later he passed into academia to better grasp the science behind music’s appeal. His dual interests, music and neuroscience, and their interplay seem to appeal to many others, as evidenced by the book’s ubiquity in like-minded media outlets over the last few months. (Try here.) This likely also reflects the fact that he has written a book comprehensible to those without any music or science training.

The book does not present a cohesive theory for how music is processed in the brain, in part because there isn’t one. Levitin’s fragmentary approach reflects the fragmentary nature of the field. But even the fragments are intriguing. Music first activates the auditory cortex. Then areas adjacent and overlapping with Broca’s interpret musical syntax. Finally the meaning of the music (the musical semantics) is delineated in the mesolimbic system, including regions near Wernicke’s area. This is hardly the whole story. The cerebellum (10% of brain weight; 50-80% of neurons) possesses direct connections from the ear. Through its connections to the basal ganglia it is implicated in rhythm and meter. How all these linkages are coordinated into the experience of music is less clear, but Levitin surely puts many of the pieces on the table.

Levitin introduces a few diseases that offer insights into the neuroscience of music. Those with higher functioning autistism are drawn to the structure of music but they miss the emotional appeal. Perhaps this is a result of their smaller neocerebellums. On the other hand, people with Williams Syndrome have larger neocerebellums and are musically gifted. Levitin casts his net wider still. Citing work done by Schmahmann et al regarding the cerebellar cognitive affective syndromes, he associates socialibility and musicality.

In later chapters, Levitin takes a more psychological approach as he explores the genesis of musical preference and the nature of expertise. In the last chapter he dives into evolutionary psychology. Where this fits into the overarching purpose of the book is not clear. Levitin supports the idea that music, or traits that endow musical ability are present today as a result of sexual selection. Here is not the place to deconstruct each of his arguments for this position. This has been done by many critics of evolutionary psychology. What is more interesting is why intelligent thinkers insist that certain traits exist as the consequence of selection, either sexual or natural. Perhaps the mantle of natural selection bestows prestige and lends credence to an area of research. Regardless, the evolution of music and musical ability as the result of sexual selection is unprovable, and moreover, it does little to advance our understanding of why some music sounds so good.

June 11, 2007

Chronic Headache

Those unfortunate to suffer from chronic headache present quite a quandary to neurologists. However, the physician can go home without persistent pain in his head. Some of these patients are curable, but many of them will not respond to therapy. This proves as frustrating to the patient as to the doctor.

A Head Case by Michael J. Nelson in the June 10, 2007 New York Times offers a brief account of one patient's (the author's) experience with chronic headache. He tries a number of medications without any relief of the headache that has plagued him for twenty years; he does experience unsettling side effects. In an act of desparation he tries novicaine scalp injections which leave him with worse pain.

This account is matched by many similar experiences of chronic headache patients. Careful, almost algorithmic approaches by enthusiastic headache specialists can yield results, but chronic pain is chronic for a reason.

May 16, 2007


The confusion in terminology surrounding this condition seems to reflect its complexity.

Oftentimes they are diagnosed in patients who have epilepsy. Along with their epilepsy they may have abnormal interictal EEGs and/or abnormal brain imaging. Therefore it becomes necessary to capture the problematic spells with an EEG to determine whether increasing or adding other antiepileptics is prudent. Usually this has already been done and not worked before a patient is admitted for EEG monitoring.

Capturing non-epileptic spells puts the physician in an uncomfortable position. To sort out what the genesis of the often medically refractory spells is requires a bit of deception. Usually the characteristics of the spells indicate to the physician whether a spell is epileptic or not. The bind is that without capturing these one can never know for sure whether they are epileptic. Unlike other psychogenic symptoms, Viz. other manifestations of somatoform disorders, pseudoseizures can be documented with a normal ictal EEG. For pseudoseizures, there is a test to prove that the somatoform disorder is not real or organic. I think the deception - if there is any - enters when the physician directs testing to gather evidence against the patient. Of course this could be viewed otherwise. By proving that the spells are not epileptic a patient can be spared potentially toxic medications and medical care not directed at the underlying problem, one more psychologic or social.

This post previously detailed what I am calling deception taken to its greatest extent. I previously didn't have a discussion of the difficulty inherent in diagnosing and treating pseudoseizures, nor did I state the unsavoriness in the following interaction. An attending told a woman with suspicious spells that he was not going to make her angry, which triggered her typical spells, but that there was another possible way to induce a seizure. A alcohol pad on the neck could cause a temperature differential and a convection that might induce a seizure. One alcohol pad was not enough so he added another. The woman became unresponsive and then began shaking. The attending took off the alcohol pad and wiped her neck with water. She stopped within a couple minutes and was very lethargic.

The most disturbing thing about this is that in identifying the spells as non-epileptic, the neurologist can walk away without having really helped the patient. The most important part of the pseudoseizure hospital admission is when the physician addresses the pseudoseizures and involves therapists and possibly psychiatrists in the patient's care. This is usually a very difficult conversation, but when done with compassion and understanding, it can be therapeutic.

January 23, 2007

The Long Sleep

From time to time a book or idea catches on in the media and you can't read a periodical without running across it. For me this has been the case with A. Roger Ekirch and his book At Day's Close: Night in Times Past.

The main idea that seems to have caught the imagination of more than one is that in times past we have slept many more hours than we do now. Without the intrusion of electric light, slumber was reached hours earlier, and it was even punctuated by a period of sleeplessness in the middle of the night. Waking up in the middle of the night is thus seen as natural and should serve as word of comfort to insomniacs everywhere. In all humans likely achieved nearly nine hours of sleep each night.

Humans are the only monophasic sleeper, that is, among mammals they are the only species with consolidated sleep. Spaniards, college students, babies, and retirees don't follow this rule. Just as omnivory approximates our natural state, so does frequent napping. The problem lies in the way we have structured the working day, or worse yet, how we have structured the medical resident's eighty-hour week.