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 When the Valium was withdrawn, her EEG again looked worse but did not show epileptic activity.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.