She's Cured?

Maude (henceforth called because of her similarity with the character of the same name from Harold & Maude, similar in her hyperkinetic movements and pacing of speech) has since had her MR Spectroscopy. It did help in characterizing whether her left temperoparietal lesion was a tumor or not. Since her lesion encompasses Wernicke's area, a biopsy was deferred as not to cause irreparable damage, because the changes seen on MRI could be post-ictal. For this reason another MRI will be obtained in a month when I will see her again in clinic.

Her hospitalization also included continuous EEG monitoring. Her untreated EEG revealed left temporal spikes and waves with left hemispheric slowing. This improved with Dilantin and a trial of Valium. When the Valium was withdrawn, her EEG again looked worse but did not show epileptic activity. She was discharged from the hospital on Dilantin and Phenobarbital. The addition of Phenobarbital allowed her the best night of sleep in some time.

Throughout her stay, her aphasia did not resolve. (I noted above that her pacing of speech was like Maude. The content was often unintelligible.) She continuously made paraphasic errors, showed difficulty with comprehension, perseverated, demonstrated some left-right confusion, but was never disoriented. Most of the time she was aware of her errors, but was unable to correct them.

Lastly by the time of discharge her arthritic pain had returned. The pain that had plagued her for years, then vanished for three weeks, was suppressed for three weeks. The correlation with her neurologic disease (whatever it is) is clear; the explanation is much less so. The fact that her pain returned with the initiation of antiepileptics suggests an answer.

She's Cured!

An elderly woman presented with acute onset of alteration of consciousness, expressive aphasia and short-lived right sided weakness. Her symptoms came on abruptly, twice in the last three weeks. The first time she was diagnosed with a stroke and effectively rehabilitated, until she had the second spell. Her EEG contains left temporal slowing and spikes suspicious for an epileptogenic focus. Her MRI reveals an abnormal area in the left posterior temporal and adjoining parietal lobe. At this time it is unclear what the lesion exactly is. An MR Spectroscopy will be performed to differentiate between an infarct or a neoplasm.

A curious element of the patient's presentation is that she no longer has the arthritic pain that plagued her for years. A condition called pain asymbolia offers a possible explanation. Pain asymbolia describes the situation in which a patient perceives a painful stimulus but is unconcerned by it and may even laugh. There is a disconnect between the perception of pain and the affective component of pain. Ramachandran hypothesizes an explanation for this phenomenon. Following integration of spinothalamic pain information in the insular cortex, there are connections with the amygdala (and from there to the limbic system) that may be disrupted, thus producing pain asymbolia. According to Ramachandran, laughter may result from the disconnect between the pain and its lack of emotional content, an organic punch-line.

However in this patient, not only is the affective component of pain absent, she has no pain at all.

Painful stimuli are modified by modulatory pathways, some of them arising in the somatosensory cortex (others arising from the hypothalamus, periaqueductal gray matter of the midbrain, the raphe nuclei, and other nuclei of the rostral ventral medulla). Perhaps a seizure can cause overactivation in one of these modulatory pathways, in this case the somatosensory cortex or one of its association areas, effectively quelling pain stimuli at the level of the spinal cord.

Ramachandran VS. A Brief Tour of Human Consciousness: From Impostor Poodles to Purple Numbers. Pi Press, New York, 2004.

Lewy Body Dementia

The New York Times Magazine ran an article today attributing Scrooge's "symptoms" to Lewy Body Dementia. (perhaps available here)

Dickens reports classic parkinsonian features such as masked facies, rigidity, shuffling gait, resting tremor in his description of Scrooge. If the visits Scrooge receives from the past, present, and future are considered visual hallucinations, his clinical picture is consistent with Lewy Body Dementia.

The article does not comment on the existence of Jiminy Cricket.

Miller-Fisher Syndrome II

I first talked about this case a few weeks ago (Nov. 25). After being staffed with the attending and undergoing a number of diagnostic tests, some consistent with the diagnosis, others not, the two-year-old is still felt to have Miller-Fisher Syndrome.

Albuminocytologic dissociation was not present. This is only expected within a day or two of onset. The LP was days later.

Abnormal enhancement of the cranial nerves was present on MRI: III, V, and VI.

GQ1b IgG antibody was negative. This is present in 90% of cases. The child never progressed to a syndrome more consistent with Bickerstaff's Brainstem Encephalitis or Guillian-Barre Syndrome. Patients with these two diagnoses can also express GQ1b antibody. No other antibody was tested in the patient.

MFS carries a good prognosis and the child was not treated. There have been no randomized trials but case series show no benefit to either IVIG or Plasma Exchange. After about 5 days in the hospital, the child left in about the same condition as when he arrived.

The Winds of Mind

Neurologic deficits have been used for years to map out areas of the brain. Two frequently cited examples are Wernicke's and Broca's aphasia. Broca's aphasia corresponds to a lesion of the posterior part of the inferior frontal gyrus and the surrounding cortex and subcortical white matter of the dominant hemisphere, while Wernicke's aphasia corresponds to a lesion involving the posterior portion of the superior temporal gyrus.

V.S. Ramachandran takes neurologic deficits from the less well charted waters of neurology to draw fascinating and important conclusions. He also makes quite a few conjectures. His book answers as many questions as it proposes. Ramachandran is suggesting a research program based on his hypotheses regarding what is really wrong in autism and schizophrenia. Commentary on the contents of this book could easily exceed its length. The numbers of ideas runs quite thick. At times I wished there were more to read. Perhaps that is Ramachandran's way of spurning people to investigate the primary sources, many of them his own.

Ultimately, by answering all the questions, by explaining all the oddball neurologic diseases and syndromes, Ramachandran hopes to unravel what makes us human, how the mind works (and fails to work), and how we should understand ourselves. To me these are the most important questions to answer, and I think we are on the way.

Ramachandran VS. A Brief Tour of Human Consciousness: From Impostor Poodles to Purple Numbers. Pi Press, New York, 2004.

Updating Cajal

The Neuron Doctrine, Redux presents the multitude of interactions among neurons and non-neuronal central nervous system cells that were not included in Cajal's original formulation.

Camillo Golgi developed the silver staining technique that allowed Santiago Ramon y Cajal (picture at right) to visualize individual neurons. His cell images allowed him to successfully argue that neurons were not intimately connected, but rather they communicated via synapses. They shared the Nobel Prize in 1906.

Techniques have improved and new ones have evolved since Golgi and Cajal were experimenting. There are (1) gated gap junctions between neurons that allow some degree of electrical transmission, (2) receptors to neuromodulatory substances outside of the synapse, (3) the presence of axon-glial communication, (4) interactions between glial cells via neurotransmitters and electrical transmission.

With 100 billion nerve cells talking, and then the multiple ways they can, the possibilities are limitless.

Ramachandran: "The number of possible permutations and combinations of brain activity, in other words the numbers of brain states, exceeds the number of elementary particles in the known universe." Bullock et al: "This suggests that the complexity of the human brain and likely other regions of the nervous system derive from some organizational features that make use of the permutations of scores of integrative variables and thousands or millions of connectivity variables."

There is, however, a higher organization of action potentials, as seen on electroencephalograms. "The permutation and combinations of brain activity" are limited by the very organizations and connections that suggest their infinite arrangements. EEG may one day emerge as an old tool answering new questions.

Bullock, T.H., Bennett, M.V.L., Johnston, D., Josephson, R., Marder, E., Fields R.D. 2005. The Neuron Doctrine, Redux, Science, V.310, p. 791-793
Ramachandran VS. A Brief Tour of Human Consciousness: From Impostor Poodles to Purple Numbers. Pi Press, New York, 2004.

Evolution Again

D. Buss again (see prior post): "Ancestral conditions that favored the dissolution of a mateship constituted a recurrent adaptive problem over human evolutionary history and thus imposed selection pressures for the evolution of strategic solutions."(p. 171) The only selection pressure was on having an intact brain. The strategies are only an outgrowth of that. Each strategy isn't a trait undergoing selective pressure.

Humans today face a completely different landscape than those at the beginning of recorded history. Any evolutionary biologist would agree that it is too short a time for significant evolution via natural selection. And yet, we operate in this changed world without much difficulty. Without any appreciation for history, one might posit that humans are evolved to operate computers: our manual dexterity to enter keystrokes, our ability to multi-task many windows at once, even our language to write HTML code. This is of course preposterous, just as most of Dr. Buss's arguments are.

I think the important question is how we are able to adapt to such varied environments? How did we become repositories of information, manipulators of tools, possessors of language? These were the skills that when applied to old problems, such as having babies, yielded the many strategies discussed in Buss's book. For another example, writing is not evolved. It is an exaption born of our ability for language, but it is writing that has made today's civilizations possible.

Dr Pangloss

The Evolution of Desire by David Buss talks about sex a lot. It comes from the group of writers and academics espousing Evolutionary Psychology. It's a sexy discipline.

This from Wikipedia and the man often mentioned in the same breath as evolutionary psychology: "Evolutionary Psychology is, to quote Steven Pinker, 'not a single theory but a large set of hypotheses' and a term which 'has also come to refer to a particular way of applying evolutionary theory to the mind, with an emphasis on adaptation, gene-level selection, and modularity.'" O boy. If it is a set of hypotheses that can't be tested, is it science? Is it truly informative? The short answer is no? I'll leave the argument against adaptationist thinking to Gould and Lewontin.

I heard about the Spandrels of San Marco in undergrad. It was not until tonight that I read the full article. The Proceedings of the Royal Society of London Biology are kind enough to offer the article here. You may only be able to access it by starting through google. Search The Proceedings of the Royal Society of London Biology. The full citation is at the bottom.

Like a choice philosophic passage or engrossing novel, this paper engages and excites. It underlines the idea that adaptionist thinking cannot be applied to the varied expressions of human behavior. Humans are the undetermined animal, as well as the exploitative animal, the opportunist, the conniver, the schemer.

In his book, Buss catalogues a variety of behaviors that in large, he considers selected adaptations. In my mind they are no more than expressions of underlying drives, their manifestation different in males and females. Human behavior is contextual. The variety is a response to different contexts. The fact that humans can display such different behaviors is testament to our freedom from biologic behavioral constraints.

1. Gould, S. J. And Lewontin, R. C., "The Spandrels of San Marco and the Panglossian Paradigm: A Critique Of The Adaptationist Programme," Proceedings Of The Royal Society of London, Series B, Vol. 205, No. 1161 (1979), Pp. 581-598.
2. Buss, David. "The Evolution of Desire: Strategies of Human Mating," 2nd Edition. NY: Basic Books, 2003.

Mirth

"He then found that if he spent time engaged in imitating the components that make up a smile, his mood lifted. 'That was like an epiphany,' he recalls." This is from the article by Siri Schubert in the current SA Mind. It discusses the work of Paul Ekman.

Laughter Clubs seem to have understood this a few years ago. Dr. Madan Kataria (laughing man on right) started the first laughing club on March 13, 1995. He now is the godfather of laughter yoga.

Jackass as therapy may take a while to gain currency.

Gelastic seizures are left out of Bradley and Daroff but they are no less real. Maybe I wasn't looking in the right place in the index. I had the opportunity to see gelastic seizure earlier this year and they are striking to say the least. The young woman appeared possessed. The laughter was quiet but maniacal. The cause of her seizures was HSV encephalitis years earlier.

"It has been suggested that normal laughter is the result of an interaction of several different brain structures: the frontal and temporal neocortex; the temporo-basal cortex; the visual, olfactorial, and auditorial associative areas; the limbic system with the cingulate gyrus; and the brainstem. The motor manifestations of laughter and the feeling of amusement or mirth have been claimed to be separable functions and, consequently, neurologically dissociated (Lopes da Silva et al 1990; Arroyo et al 1993). Gelastic seizures have been observed to be associated with many different conditions: mainly hypothalamic hamartomas, but also as a seizure manifestation in connection with temporal and frontal lobe lesions as well as other focalities." link

Laughter and mirth may be "neurologically dissociated", but one can not emulate laughter without feeling happy.

Miller-Fisher Syndrome

Miller-Fisher Syndrome Miller-Fisher Syndrome is considered a variant of Guillain-Barre Syndrome. It is characterized by ophthalmoplegia, ataxia, and areflexia.

As a resident I was called to see a 2-year-old with the rapid onset of ptosis. At least this is how it was described by the outside doctor. He also noted that the child had difficulty walking. With this information, he considered myasthenia.

The child had a upper respiratory infection 4-5 days prior to presenting. Otherwise he was in good health. The night before he presented, the mother noted that he had very wide eyes. In the morning the child had drooping eyes and difficulty walking. With these symptoms the mother brought him to the outside hospital.

On exam, the child's eyes were very wide with slowly drooping eyelids. Once the eyes were closed they snapped back open. His eyes were always in a midline position. Pupils were reactive. With testing, the child was unable to move his eyes horizontally and upward gaze also seemed impaired. His gait was markedly unsteady. He appeared as if he were aboard a ship. His strength, as much as can be tested in a 2-year-old, seemed normal. Reflexes were absent.

Clinically, this is a case of MFS. An LP and GQ1b antibodies will be obtained to make the definitive diagnosis. The LP should show albuminocytologic dissociation If the patient's condition worsens, plasma exchange or IVIG can be given, but the condition is considered benign, and usually completely resolves.

Frontotemporal Dementia

Alois Alzheimer famously described a case of a 51-year-old female with delusions and memory impairment in a 1907 paper. His observations were coupled with his neuropathological findings of neuritic plaques and neurofibrillary tangles, the pathologic hallmarks of the disease. Originally used to describe a rare form of pre-senile dementia, those who suffer from Alzheimer's Disease are mainly elderly patients with functional decline in memory, language, visuospatial function, and executive function.

Frontotemporal Dementias affect less patients but the results are equally if not more devastating. Age of onset is usually around 50 to 60. The causes are heterogeneous. As the name suggests, frontotemporal dementias are marked by a preponderance of atrophy in the frontal and temporal lobes. Bifrontal atrophy leads to disinhibition and socially inappropriate behavior. Depending on the location of atrophy, varying degrees of aphasia, semantic dementia, prosopagnosia, and limb apraxia can be seen. FTD can present as a progressive behavioral disturbance or a progressive language disturbance. Among those exhibiting the latter, disinhibition, overactivity, and restlessness are associated with prominent orbitofrontal involvement. Loss of motivation is associated with dorsolateral frontal involvement.

A female with a psychiatric history was admitted from an outside hospital. Her illness began when she was 53: she was hospitalized in a psychiatric hospital for frank delusions. She is now 61 with marked dementia. She cannot form new memories; she exhibits diffuse hyperreflexia with upgoing toes bilaterally; she has a tendency to retropulse; she perseverates and cannot be redirected easily. Her age and severe cognitive impairment together with long-tract signs suggest FTD, although the length of her course argues against it. She is no longer in contact with her family and her caretaker is no longer able to manage her at home.