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Neurological Sciences : Official... Jul 2014Cosimo I de' Medici (1519-1574) was the first Grand Duke of Tuscany. He was one of the most important members of the Medici family. He was an excellent conqueror and a...
Cosimo I de' Medici (1519-1574) was the first Grand Duke of Tuscany. He was one of the most important members of the Medici family. He was an excellent conqueror and a good politician. Moreover, he was able to attract and encourage artists, scientists and architects to promote Florence as the cultural capital of the Italian Renaissance. Historical chronicles report that he suffered from a stroke when he was 49 years old. Together with the acute manifestation of stroke, he displayed peculiar symptoms. He had gait disturbances and sphincter dysfunctions. His language became poor and hard to understand. His mood was very fluctuating and in the last years of his life he was a short-tempered man. In addition, he had a characteristic symptom, so-called pathological laughing and crying. The course of his disease was slow and stuttering. Taken together, these data seem to be one of the first reports of pseudobulbar paralysis. The disease of Cosimo I was probably due to a chronic cerebral vasculopathy, known as small vessels disease. We discuss this hypothesis regarding an ancient clinical case, with the support of current studies.
Topics: History, 16th Century; History, Medieval; Humans; Italy; Male; Middle Aged; Pseudobulbar Palsy; Risk Factors; Stroke
PubMed: 24604411
DOI: 10.1007/s10072-014-1694-8 -
Brain and Nerve = Shinkei Kenkyu No... Nov 2008Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant vascular encephalopathy that has been... (Review)
Review
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant vascular encephalopathy that has been mainly reported in Europe and the United States. Recently, this disease has been reported in Japan and the increasing number of reported cases has been attracting attention. Currently, the clinical diagnosis of CADASIL is based on the satisfaction of the following conditions: (1) development of the condition at a relatively young age (40-50 years), (2) no risk for stroke, (3) repeated attacks of lacunar infarction with gradual progression to pseudobulbar paralysis and dementia (migraine, emotional disturbance, cerebral infarction, and dementia in 30%, 20%, 85%, and 30-90% of patients, respectively), and (4) family members with similar symptoms (autosomal dominant inheritance). The diagnosis is also established on the basis of the following findings of imaging and laboratory studies: the presence of (1) leukoaraiosis and multiple small infarcts in the bilateral deep white matter, basal ganglia, thalamus, and pons revealed by MRI; (2) granular osmiophilic material (GOM) around the vascular smooth muscles in the brain, skeletal muscle, peripheral nerves, and skin demonstrated by electron microscopy; and (3) Notch3 mutations revealed by DNA analysis. Characteristics of CADASIL patients in Japan: Between 1997 and 2008, 38 CADASIL families have been reported in Japan. The age at onset of local neurological symptoms ranged from 15 to 71 years (mean 42. 3 +/- 11.4 years). All patients except one with borderline hypertension were normotensive or hypotensive. Out of 45 patients, 18 (40%) had migraine; 37 (82.2%) had repeated cerebral ischemic attacks including transient ischemic attacks (TIA); and 22 (48.9%), including borderline cases, had intellectual impairment. Nine of 38 patients (23.7%) had pseudobulbar paralysis. The retinal arteries were narrowed in 4 of 16 patients. The patients were distributed nationwide. Mutations in exon 4 have been reported in 22 of 31 families (71%). It is expected that an increase in the number of reported cases will lead to the discovery of other mutations associated with this condition. The mechanism of development of CADASIL due to Notch3 mutations is still unknown. However, a recent study has revealed that the Notch3 ectodomain is a major component of GOM. On binding to its ligand, Notch3 normally undergoes proteolytic cleavage, resulting in the clearance of the extracellular domain. However, in CADASIL, it accumulates as GOM and potentially inhibit the normal metabolism of smooth muscle cells.
Topics: Adult; Anticoagulants; Brain; CADASIL; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Smooth, Vascular; Mutation; Piperazines; Platelet Aggregation Inhibitors; Prognosis; Receptor, Notch3; Receptors, Notch
PubMed: 19069156
DOI: No ID Found -
The American Journal of Managed Care Dec 2017Pseudobulbar affect (PBA), despite its prevalence and distinctive symptoms, is widely underrecognized and undertreated. It is characterized by uncontrollable laughing or... (Review)
Review
Pseudobulbar affect (PBA), despite its prevalence and distinctive symptoms, is widely underrecognized and undertreated. It is characterized by uncontrollable laughing or crying that can occur in an exaggerated manner or inappropriately to a given situation or stimuli. PBA is thought to center around preexisting neurological conditions, which include Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, traumatic brain injury, and stroke. The PBA Registry Series trial was created to measure the prevalence of PBA among patients with these underlying neurological conditions. Through greater awareness, recognition, and diagnosis, treatment for patients with PBA can be improved.
Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Female; Humans; Male; Middle Aged; Nervous System Diseases; Parkinson Disease; Prevalence; Pseudobulbar Palsy; Quality of Life; Risk Assessment; Severity of Illness Index; United States
PubMed: 29297656
DOI: No ID Found -
La Revue Du Praticien Feb 1980
Topics: Amyotrophic Lateral Sclerosis; Bulbar Palsy, Progressive; Cerebrovascular Disorders; Deglutition Disorders; Diagnosis, Differential; Facial Paralysis; Humans; Phonation; Voice Disorders
PubMed: 7361040
DOI: No ID Found -
Acta Neuropsychiatrica Apr 2012Palilalia is an acquired speech disorder characterised by involuntary and spontaneous repetition of words or phrases two or more times in a row. It can occur in a...
INTRODUCTION
Palilalia is an acquired speech disorder characterised by involuntary and spontaneous repetition of words or phrases two or more times in a row. It can occur in a variety of disorders including postencephalic parkinsonism, pseudobulbar palsy, schizophrenia, Gilles de la Tourette syndrome and others.
CLINICAL CASE
We describe a case of a 28-year-old man with refractory schizophrenia that developed palilalia with 300 mg of clozapine. In the patient evaluation we found unspecific alterations in the electroencephalogram, with normal blood tests and cerebral magnetic resonance imaging. Palilalia disappeared with lowering doses of clozapine.
DISCUSSION
The appearance of palilalia induced by clozapine is a rare pharmacologic side-effect which physicians should be familiarised with when evaluating this symptom presentation.
PubMed: 26952954
DOI: 10.1111/j.1601-5215.2011.00594.x -
Expert Review of Neurotherapeutics Jul 2011Pseudobulbar affect (PBA) consists of uncontrollable outbursts of laughter or crying inappropriate to the patient's external circumstances and incongruent with the... (Review)
Review
Pseudobulbar affect (PBA) consists of uncontrollable outbursts of laughter or crying inappropriate to the patient's external circumstances and incongruent with the patient's internal emotional state. Recent data suggest disruption of cortico-pontine-cerebellar circuits, reducing the threshold for motor expression of emotion. Disruption of the microcircuitry of the cerebellum itself may likewise impair its ability to act as a gate-control for emotional expression. Current evidence also suggests that serotonergic and glutamatergic neurotransmission play key roles. Although antidepressants have shown benefit, the supportive clinical data have often derived from small numbers of patients and unvalidated measures of PBA severity. Dextromethorphan/quinidine, the first FDA-approved PBA medication, is a novel therapy with antiglutamatergic actions. As life expectancy lengthens and the neurologic settings of PBA become more common, the need for treatment can be expected to increase.
Topics: Adrenergic alpha-Antagonists; Brain; Clinical Trials as Topic; Crying; Dextromethorphan; Excitatory Amino Acid Antagonists; Humans; Laughter; Pseudobulbar Palsy; Quinidine; Synaptic Transmission
PubMed: 21539437
DOI: 10.1586/ern.11.68 -
Archives of Internal Medicine Feb 1965
Topics: Brain Diseases; Bulbar Palsy, Progressive; Cerebrovascular Disorders; Diabetic Neuropathies; Diagnosis; Humans; Paralysis
PubMed: 14332003
DOI: 10.1001/archinte.1965.03860140078017 -
Drugs of Today (Barcelona, Spain : 1998) Sep 2008A new agent containing a combination of dextromethorphan (DM) and quinidine (Q) is currently under development for the treatment of pseudobulbar affect (PBA). PBA is a... (Review)
Review
A new agent containing a combination of dextromethorphan (DM) and quinidine (Q) is currently under development for the treatment of pseudobulbar affect (PBA). PBA is a disorder of emotional regulation, characterized by uncontrollable outbursts of laughing and/or crying that are disproportionate to the emotions being experienced. The pathophysiology of PBA is currently unknown, although the disorder is thought to occur exclusively in the setting of neurological disease. The most influential theory on PBA posits that emotional outbursts are being generated autonomously in the brain stem due to loss of regulatory control by the frontal lobe. Although rarely life-threatening, PBA can have significant impact on patient quality of life, and thus merits treatment. There are currently no approved treatments for PBA. Several agents have been found to be effective in small placebo-controlled trials and case series, with the most commonly used agents being tricyclic antidepressants and selective serotonin reuptake inhibitors. Both these treatments are inexpensive and relatively low-risk, although the quality and quantity of data available on their efficacy are not optimal. DM has several pharmacological mechanisms of action relevant to the brain. It is an N-methyl-D-aspartate (NMDA) receptor antagonist, which prompted investigators to study its potential for slowing progression in amyotrophic lateral sclerosis (ALS), where glutamate toxicity is thought to be a factor. The combination agent DM/Q was developed to slow the metabolism of DM by P450 2D6 enzymes in the liver. DM/Q was not effective in slowing ALS progression, but patients noted that it helped to control their emotional outbursts, suggesting it might be useful as a treatment for PBA. DM is also a sigma-1 receptor agonist. These receptors are widely distributed in the brain, but probably most heavily in the limbic system, suggesting that DM may exert its emotion-controlling effects via these receptors. The endogenous ligands for sigma-1 receptors are not altogether known, although they appear to include gonadal steroids. DM/Q was recently shown to be effective in reducing the severity of PBA in two large studies of ALS and multiple sclerosis, which are probably the most common neurological settings. These are the largest treatment studies of PBA ever done. The agent was safe and relatively well tolerated. Further studies are being conducted to see if efficacy can be maintained with lower doses of quinidine. If DM/Q is approved by the U.S. Food and Drug Administration for treatment of PBA, it would be the first agent approved for this purpose. Currently, the antidepressants are probably the most attractive pharmacologic options for treatment of PBA. The choice of whether to use DM/Q in this setting will likely depend on individual patient factors as well as cost.
Topics: Antidepressive Agents, Tricyclic; Clinical Trials as Topic; Dextromethorphan; Drug Combinations; Humans; Pseudobulbar Palsy; Quinidine; Selective Serotonin Reuptake Inhibitors
PubMed: 19137121
DOI: 10.1358/dot.2008.44.9.1258664