Archive for January, 2011

AGING AND POWERFUL MINDS IN HISTORY: LEADERSHIP AND DEMENTIA

Saturday, January 29th, 2011
To fully appreciate the force of these facts, let us also make note of their universal nature. The art is not the only arena in which the masters of their crafts retain their touch despite the crippling effects of the assorted brain diseases of aging. Let us also consider the arena of statesmanship and politics. And here we are stepping into a morally agnostic territory. If the great artists are remembered for their good, at least as public personas, then the important statesmen and politicians can be either heroes or villains, or tangled juxtapositions of both. We will consider examples of all of the above among those aspiring to rule despite their cognitive decline and even early dementia.
“First among the virtues found in the state, wisdom comes into view,” wrote Plato in his Republic. We wish! We often think of the rich and the powerful as exempt from the laws of nature, including the laws of physics and biology. What’s more, the rich and the powerful are probably the first to share this belief. This is benevolently known by some as “boundless self-confidence” and less benevolently by others as “hubris.”
But whatever may or may not be true for other natural laws, the biological processes causing dementia do not discriminate on the basis of wealth, power, or even moral rectitude. We are only beginning to understand dementia’s biological causes and the processes by which it robs the mind of its powers and turns the most brilliant intellect into a shell, an incoherent and confused wreckage of a human being. Many forms of dementia exist, some causing gradual brain atrophy and others causing a gradual accumulation of small strokes. To make matters worse, they often appear in combinations. All dementias are equal-opportunity scourges, eroding the mind in a variety of insidious ways, without sparing the rich, the powerful, and the righteous. It is amazing how many history-shaping decisions have been made, and continue to be made, by eroding, even dementing minds before the eyes of a power-awed, unsuspecting public.
This thought first crossed my mind many years ago, as I was making my diagnosis of Ronald Reagan. A refugee from the former Soviet Union, I had been an anomaly among my friends in the liberal New York intelligentsia as an admirer of Reagan, the man who helped dismantle the “evil empire” I had fled half a lifetime ago. So, when the inkling of Reagan’s dementia first crossed my mind, I was far from gloating; I was genuinely upset. That was well before Reagan’s Alzheimer’s disease became pub-he knowledge or even a matter of public speculation. In fact, it was well before Reagan left the White House.
Sometime during his second term, Reagan was quizzed by a journalist about the wreath-laying Bitburg affair, when in 1985 Reagan honored a cemetery full of Nazi SS guards against the advice of his aides. The feeling was that the American president was being manipulated by the then West German chancellor Helmut Kohl, who needed the gesture for his own political ends. As I was watching the interview on TV, Reagan’s responses to the journalist’s questions sounded so staggeringly incoherent that I picked up the phone, called my neurosurgeon friend (and a fellow foreign affairs buff) Jim Hughes, and said: “Reagan has Alzheimer’s!” Jim laughed, not realizing that I meant it literally, and not as a figure of speech.
This may have sounded like a snap judgment, gratuitous even, but I was better equipped for making it than most people. A neuropsychologist with (then) almost twenty years of clinical experience and a reputation for diagnostic acumen, I make a living by studying, diagnosing, and treating various brain diseases affecting the mind. I was also doing research, publishing scientific papers, and writing books about the brain and the mind, and the numerous ways in which they may go wrong. The incoherence that so struck me in Reagan’s responses would have raised my diagnostic antennae coming from anyone, and Ronald Reagan was not exempt.
My hunch about Reagan was strengthened some time later, during the last day of his presidency, as I was watching George Bush’s inauguration on TV. Reagan walked past the honor guard, approached the imposing leather chair prepared for him, slumped into the chair, and was immediately asleep, his head dropping on his chest instantaneously. “Brain stem gone,” I said to myself, alluding to the part of the brain that is in charge of maintaining the arousal necessary for sound mental activities. At this point I was convinced that a significant portion of Reagan’s second term had taken place in the shadow of his slippage toward early dementia.
My conclusion that Ronald Reagan was suffering from Alzheimer’s disease or a similar dementing condition was sealed soon after he left office and well before the first official intimation to that effect. As I was watching Reagan’s interviews about the Iran-Contra affair, I was impressed, almost shocked, by the sincerity of his denial of any memories of the events, by the befuddled and incredulous expression on his face when the events and names of people were being thrown at him by the interviewers. Contrary to the opinion of many commentators, I was convinced that Reagan was not dissembling, that he was not attempting to hide anything. With the confidence of an experienced clinician, I felt that he truly did not remember. Ronald Reagan was suffering from early dementia.
Of course, my diagnosis via television was subsequently confirmed when the “official” diagnosis was made in 1994 at Mayo Clinic, and Reagan’s hereditary risk factors revealed (both his mother and older brother had suffered from dementia).The former president’s own courageous admission of his illness earned him my respect and that of many other people. Were my earlier observations of Ronald Reagan indicative of outright dementia, or did they still belong in the gray area of “neuroerosion” or “mild cognitive impairment,” the early prodrome of things to come? Ultimately, this is a matter of semantics more than of substance, since we are talking about a gradual downslide devoid of discrete boundaries and not about an abrupt transition, a decline that came to an end in 2004, ten years after the “official” diagnosis of dementia and considerably longer after it had actually begun to set in.
*12\302\2*

AGING AND POWERFUL MINDS IN HISTORY: LEADERSHIP AND DEMENTIATo fully appreciate the force of these facts, let us also make note of their universal nature. The art is not the only arena in which the masters of their crafts retain their touch despite the crippling effects of the assorted brain diseases of aging. Let us also consider the arena of statesmanship and politics. And here we are stepping into a morally agnostic territory. If the great artists are remembered for their good, at least as public personas, then the important statesmen and politicians can be either heroes or villains, or tangled juxtapositions of both. We will consider examples of all of the above among those aspiring to rule despite their cognitive decline and even early dementia.”First among the virtues found in the state, wisdom comes into view,” wrote Plato in his Republic. We wish! We often think of the rich and the powerful as exempt from the laws of nature, including the laws of physics and biology. What’s more, the rich and the powerful are probably the first to share this belief. This is benevolently known by some as “boundless self-confidence” and less benevolently by others as “hubris.”But whatever may or may not be true for other natural laws, the biological processes causing dementia do not discriminate on the basis of wealth, power, or even moral rectitude. We are only beginning to understand dementia’s biological causes and the processes by which it robs the mind of its powers and turns the most brilliant intellect into a shell, an incoherent and confused wreckage of a human being. Many forms of dementia exist, some causing gradual brain atrophy and others causing a gradual accumulation of small strokes. To make matters worse, they often appear in combinations. All dementias are equal-opportunity scourges, eroding the mind in a variety of insidious ways, without sparing the rich, the powerful, and the righteous. It is amazing how many history-shaping decisions have been made, and continue to be made, by eroding, even dementing minds before the eyes of a power-awed, unsuspecting public.This thought first crossed my mind many years ago, as I was making my diagnosis of Ronald Reagan. A refugee from the former Soviet Union, I had been an anomaly among my friends in the liberal New York intelligentsia as an admirer of Reagan, the man who helped dismantle the “evil empire” I had fled half a lifetime ago. So, when the inkling of Reagan’s dementia first crossed my mind, I was far from gloating; I was genuinely upset. That was well before Reagan’s Alzheimer’s disease became pub-he knowledge or even a matter of public speculation. In fact, it was well before Reagan left the White House.Sometime during his second term, Reagan was quizzed by a journalist about the wreath-laying Bitburg affair, when in 1985 Reagan honored a cemetery full of Nazi SS guards against the advice of his aides. The feeling was that the American president was being manipulated by the then West German chancellor Helmut Kohl, who needed the gesture for his own political ends. As I was watching the interview on TV, Reagan’s responses to the journalist’s questions sounded so staggeringly incoherent that I picked up the phone, called my neurosurgeon friend (and a fellow foreign affairs buff) Jim Hughes, and said: “Reagan has Alzheimer’s!” Jim laughed, not realizing that I meant it literally, and not as a figure of speech.This may have sounded like a snap judgment, gratuitous even, but I was better equipped for making it than most people. A neuropsychologist with (then) almost twenty years of clinical experience and a reputation for diagnostic acumen, I make a living by studying, diagnosing, and treating various brain diseases affecting the mind. I was also doing research, publishing scientific papers, and writing books about the brain and the mind, and the numerous ways in which they may go wrong. The incoherence that so struck me in Reagan’s responses would have raised my diagnostic antennae coming from anyone, and Ronald Reagan was not exempt.My hunch about Reagan was strengthened some time later, during the last day of his presidency, as I was watching George Bush’s inauguration on TV. Reagan walked past the honor guard, approached the imposing leather chair prepared for him, slumped into the chair, and was immediately asleep, his head dropping on his chest instantaneously. “Brain stem gone,” I said to myself, alluding to the part of the brain that is in charge of maintaining the arousal necessary for sound mental activities. At this point I was convinced that a significant portion of Reagan’s second term had taken place in the shadow of his slippage toward early dementia.My conclusion that Ronald Reagan was suffering from Alzheimer’s disease or a similar dementing condition was sealed soon after he left office and well before the first official intimation to that effect. As I was watching Reagan’s interviews about the Iran-Contra affair, I was impressed, almost shocked, by the sincerity of his denial of any memories of the events, by the befuddled and incredulous expression on his face when the events and names of people were being thrown at him by the interviewers. Contrary to the opinion of many commentators, I was convinced that Reagan was not dissembling, that he was not attempting to hide anything. With the confidence of an experienced clinician, I felt that he truly did not remember. Ronald Reagan was suffering from early dementia. Of course, my diagnosis via television was subsequently confirmed when the “official” diagnosis was made in 1994 at Mayo Clinic, and Reagan’s hereditary risk factors revealed (both his mother and older brother had suffered from dementia).The former president’s own courageous admission of his illness earned him my respect and that of many other people. Were my earlier observations of Ronald Reagan indicative of outright dementia, or did they still belong in the gray area of “neuroerosion” or “mild cognitive impairment,” the early prodrome of things to come? Ultimately, this is a matter of semantics more than of substance, since we are talking about a gradual downslide devoid of discrete boundaries and not about an abrupt transition, a decline that came to an end in 2004, ten years after the “official” diagnosis of dementia and considerably longer after it had actually begun to set in.*12\302\2*

INFECTIOUS DISEASES: MALARIA – WIDESPREAD DISEASE

Friday, January 14th, 2011
An infectious disease caused by a parasite known as the “Plasmodium” and transmitted by infected mosquitoes of the Anopheles family; several forms of malaria are known. At least four different Plasmodia have been associated with human malaria. These Plasmodia get into the red blood cells and ultimately destroy them. As a part of the process, malarial chills or paroxysms occur, giving rise to the different forms of malaria – the types that are irregular, the types that come regularly every two, three, or four days. A typical malarial paroxysm begins with a feeling of coldness, then of heat and finally of sweating. New drugs have been discovered which are extremely effective against malaria. Most of them are related to quinine. Malaria is probably the most widespread disease in the world. It can be controlled through control of the mosquitoes that spread it. Such control involves the cleaning up of swamps, removal of excess rain water, spraying of areas with oils or insecticides that destroy the mosquito in various stages. People who are constantly exposed to malaria in tropical areas take either quinine or the new drugs every day one hour before sunset. They screen their beds at night and keep the air moving to get rid of the mosquitoes. During the day suitable clothing is worn to prevent access of the mosquito to the skin.
*29/318/5*

INFECTIOUS DISEASES: MALARIA – WIDESPREAD DISEASEAn infectious disease caused by a parasite known as the “Plasmodium” and transmitted by infected mosquitoes of the Anopheles family; several forms of malaria are known. At least four different Plasmodia have been associated with human malaria. These Plasmodia get into the red blood cells and ultimately destroy them. As a part of the process, malarial chills or paroxysms occur, giving rise to the different forms of malaria – the types that are irregular, the types that come regularly every two, three, or four days. A typical malarial paroxysm begins with a feeling of coldness, then of heat and finally of sweating. New drugs have been discovered which are extremely effective against malaria. Most of them are related to quinine. Malaria is probably the most widespread disease in the world. It can be controlled through control of the mosquitoes that spread it. Such control involves the cleaning up of swamps, removal of excess rain water, spraying of areas with oils or insecticides that destroy the mosquito in various stages. People who are constantly exposed to malaria in tropical areas take either quinine or the new drugs every day one hour before sunset. They screen their beds at night and keep the air moving to get rid of the mosquitoes. During the day suitable clothing is worn to prevent access of the mosquito to the skin.*29/318/5*

DIAGNOSIS AND THERAPY OF HERPES SIMPLEX VIRUS (HSV) ENCEPHALITIS

Monday, January 3rd, 2011
Diagnosis
Routine diagnostic tests are of limited utility in HSV type 1 encephalitis. Examination of cerebrospinal fluid (CSF) often shows a mononuclear cell pleocytosis (10 to 1000 cells/mm3), an elevated protein concentration, and a normal or slightly low glucose level. The most helpful CSF finding, if present, is red blood cells in the absence of a traumatic lumbar puncture. This suggests necrotizing HSV type 1 encephalitis in the appropriate clinical setting. MRI with enhancement demonstrates lesions earlier than computed tomographic scan and is superior in localizing lesions to the orbital-frontal and temporal lobes. The EEG pattern in HSV type 1 encephalitis is distinctive and consists of periodic sharp-and-slow wave complexes emanating from the temporal lobe that occur at regular intervals of 2 to 3 seconds. These discharges can be unilateral or bilateral and are seen in two thirds of pathologically proven cases of HSV encephalitis. Although clinical and imaging studies can suggest HSV type 1 encephalitis, the diagnosis is correct only approximately 50% of the time when based on these criteria. Therefore, laboratory confirmation of the diagnosis is required. Polymerase chain reaction (PCR) on CSF for HSV type 1 is the procedure of choice, and results can be obtained in 1 hour. In one series, PCR was shown to be 98% sensitive and 100% specific. Serum antibodies are unhelpful, and CSF viral culture has low sensitivity. Cerebral biopsy with virus isolation has been the gold standard for diagnosis. It is rarely indicated unless CSF abnormalities are atypical, a CSF PCR study is negative, MRI and EEG are nonspecific, or clinical course is progressive despite acyclovir therapy. If CSF PCR is not available, early stereotactic brain biopsy is favored over empiric antiviral treatment, since the clinical diagnosis is only 50% accurate and alternative treatable diagnoses are found in as many as 15% of cases when biopsy is performed.
Therapy
Acyclovir is the treatment of choice for herpes encephalitis and should be instituted upon suspicion of the disease. The effects of the illness can be significantly reduced if acyclovir is begun before there is a major alteration in the patient’s level of consciousness. Therapy has reduced the mortality rate to 19% (versus 70% in untreated control subjects), with 38% of patients returning to normal function. The recommended dose is 10 mg/kg intravenously every 8 hours for 10 to 14 days. The dose should be adjusted in patients with renal failure. Patients with a Glasgow Coma Score below 6 at the beginning of therapy, age older than 30 years, or the presence of encephalitis for more than 4 days before the initiation of treatment have a very poor outcome.
Patients who survive herpes encephalitis may have severe, debilitating sequelae, including motor and sensory deficits, aphasia, and problems with cognitive function. Relapse of encephalitis is occasionally seen 1 week to 3 months after completion of acyclovir therapy and initial improvement. Retreatment with acyclovir or acyclovir and vidarabine is indicated in these cases.
*22/348/5*

DIAGNOSIS AND THERAPY OF HERPES SIMPLEX VIRUS (HSV) ENCEPHALITISDiagnosis Routine diagnostic tests are of limited utility in HSV type 1 encephalitis. Examination of cerebrospinal fluid (CSF) often shows a mononuclear cell pleocytosis (10 to 1000 cells/mm3), an elevated protein concentration, and a normal or slightly low glucose level. The most helpful CSF finding, if present, is red blood cells in the absence of a traumatic lumbar puncture. This suggests necrotizing HSV type 1 encephalitis in the appropriate clinical setting. MRI with enhancement demonstrates lesions earlier than computed tomographic scan and is superior in localizing lesions to the orbital-frontal and temporal lobes. The EEG pattern in HSV type 1 encephalitis is distinctive and consists of periodic sharp-and-slow wave complexes emanating from the temporal lobe that occur at regular intervals of 2 to 3 seconds. These discharges can be unilateral or bilateral and are seen in two thirds of pathologically proven cases of HSV encephalitis. Although clinical and imaging studies can suggest HSV type 1 encephalitis, the diagnosis is correct only approximately 50% of the time when based on these criteria. Therefore, laboratory confirmation of the diagnosis is required. Polymerase chain reaction (PCR) on CSF for HSV type 1 is the procedure of choice, and results can be obtained in 1 hour. In one series, PCR was shown to be 98% sensitive and 100% specific. Serum antibodies are unhelpful, and CSF viral culture has low sensitivity. Cerebral biopsy with virus isolation has been the gold standard for diagnosis. It is rarely indicated unless CSF abnormalities are atypical, a CSF PCR study is negative, MRI and EEG are nonspecific, or clinical course is progressive despite acyclovir therapy. If CSF PCR is not available, early stereotactic brain biopsy is favored over empiric antiviral treatment, since the clinical diagnosis is only 50% accurate and alternative treatable diagnoses are found in as many as 15% of cases when biopsy is performed.
TherapyAcyclovir is the treatment of choice for herpes encephalitis and should be instituted upon suspicion of the disease. The effects of the illness can be significantly reduced if acyclovir is begun before there is a major alteration in the patient’s level of consciousness. Therapy has reduced the mortality rate to 19% (versus 70% in untreated control subjects), with 38% of patients returning to normal function. The recommended dose is 10 mg/kg intravenously every 8 hours for 10 to 14 days. The dose should be adjusted in patients with renal failure. Patients with a Glasgow Coma Score below 6 at the beginning of therapy, age older than 30 years, or the presence of encephalitis for more than 4 days before the initiation of treatment have a very poor outcome.Patients who survive herpes encephalitis may have severe, debilitating sequelae, including motor and sensory deficits, aphasia, and problems with cognitive function. Relapse of encephalitis is occasionally seen 1 week to 3 months after completion of acyclovir therapy and initial improvement. Retreatment with acyclovir or acyclovir and vidarabine is indicated in these cases.*22/348/5*