Motor symptoms, extrapyramidal

Qll Other neuroleptic agents include phenothiazines, such as chlorpromazine, promazin and thioridazine, and thioxanthines, such as flupenthixol. The non-specific blockade of dopaminergic receptors afforded by these drugs leads to development of side effects, such as endocrine dysfunction and extrapyramidal motor symptoms. The unwanted antagonism of motor tracts results in extrapyramidal side effects, such as Parkinsonism and tardive dyskinesia. The latter is associated with involuntary movements of the face, limbs and trunk. Chronic neuroleptic therapy can inhibit the release of GABA. This in turn leads to changes in mobility. 

Fig. 19.3 Sagittal brain section illustrating dopaminergic pathways. I. Mesolimbic pathway (overactive in psychotic illness according to the dopamine hypothesis of schizophrenia).VTA= ventrotegmental area. 2. Nigrostriatal pathway (involved in motor control, underactive in Parkinson s Disease and associated with extrapyramidal motor symptoms). 3. Tuberoinfundibular pathway (inhibits prolactin release from the hypothalamus).

A 69-year-old man with bipolar disorder, who had been taking venlafaxine up to 337.5 mg daily, thioridazine 25 mg at night, and sodium valproate 1.2 g daily for several months with no adverse motor symptoms, experienced extrapyramidal effects 3 to 4 days after the venlafaxine had been gradually replaced by nortriptyline 50 mg daily. Symptoms persisted despite withdrawal of thioridazine, but improved on reduction of the nortriptyline dosage to 20 mg daily. The cause of the reaction was not known, but it was suggested that there may have been an interaction between venlafaxine and nortriptyline possibly modulated by thioridazine or sodium valproate. 

Similar findings were reported by Haberland et al. (1971) in another severely impaired patient, untreated until diagnosis at age 13, who died of pneumonia at age 25. This patient had severe mental retardation, extrapyramidal motor symptoms, and epilepsy. Microcephaly, cerebral cortical neuronal degeneration, cerebral white matter atrophy and sclerosis, and cerebellar findings similar to Crome s case were described. In addition, these anthors reported abnormal levels of glycoproteins and glycolipids. 

In addition to the direct toxic effects of copper, in certain brain areas, as in the pineal gland, ATP7B is expressed and functionally active (Boijigin et al., 1999). Glucose metabolism, especially in striatal and cerebellar areas, is disturbed in patients with WD and correlates with the severity of extrapyramidal motor symptoms. The most severe cases are characterized by the lowest consumption in the striatal area. When there is marked improvement of extrapyramidal motor symptoms impaired glucose consumption reveals a persistent brain lesion (Hermann et al., 2002). 

Phenothiazines may cause sedation, orthostatic hypotension, and extrapyramidal symptoms (EPS) such as dystonia (involuntary muscle contractions), tardive dyskinesia (irreversible and permanent involuntary movements), and akathisia (motor restlessness or anxiety).1,21,22 Chronic phenothiazine use has been associated with EPS, but single doses have also caused these effects.23... 

Most antipsychotics and especially the piperazines and the butyrophenones can cause extrapyra-midal symptoms. Blockade of dopamine receptors mainly in the corpus striatum is held responsible for these extrapyramidal effects. They may become manifest as a variety of clinical symptoms and it should be noted that within 24 8 hours after the beginning of treatment acute dystonic reactions like torticollis, facial grimacing and opisthotonos may occur. Parkinsonism-like symptoms such as bradyki-nesia, rigidity and tremor occur after weeks or months of therapy and are more common in the elderly. Motor restlessness, i.e. akathisia, also mostly occurs not before weeks or months after starting therapy. The tendency of an antipsychotic agent to produce extrapyramidal symptoms appears to be inversely related to its ability to block cholinergic receptors. 

Extrapyramidal symptoms may appear as akathisia (motor restlessness) and dystonias torticollis (neck muscle spasm), opisthotonos (rigidity of back muscles), and oculogyric crisis (rolling back of eyes),... 

Extrapyramidal symptoms appear to be dose-related and typically occur in the first few days of therapy. Marked drowsiness and lethargy, excessive salivation, and fixed stare occur frequently Less common reactions include severe akathisia (motor restlessness) and acute dystonias (such as torticollis, opisthotonos, and oculogyric crisis). 

Long-term therapy may produce extrapyramidal symptoms, such as dystonia (abnormal movements), pronounced motor restlessness, and parkinsonism. 

When D2 receptors are blocked in the nigrostriatal DA pathway, it produces disorders of movement that can appear very much like those in Parkinson s disease this is why these movements are sometimes called drug-induced parkinsonism (Fig. 11 —4). Since the nigrostriatal pathway is part of the extrapyramidal nervous system, these motor side effects associated with blocking of D2 receptors in this part of the brain are sometimes also called extrapyramidal symptoms, or EPS. 

Polyneuropathy with both sensory and motor involvement is much more common among cancer patients than pure SN [83, 110, 111]. SCLC is the most common associated tumor, although other solid tumors may be found [112]. Sensory-motor neuropathy is a quite common paraneoplastic feature in patients with onconeural antibodies, especially Hu and CRMP-5 antibodies. The CRMP-5 antibody is particularly associated with SCLC and thymoma [30]. The CRMP-5 antibody binds to oligodendrocytes as well as to neurons in specific brain regions and the retina and Schwann cells of the peripheral nervous system. In accordance with this, the clinical characteristics are heterogeneous. Many patients exhibit mixed axonal and demye-linating sensory-motor neuropathy, optic neuritis, or cerebellar dysfynction [85, 113], as well as extrapyramidal symptoms (Chapter 5.3). 

Extrapyramidal effects Parkinsonian symptoms, akathisia (motor restlessness), and tardive dyskinesia (inappropriate postures of the neck, trunk, and limbs) occur with chronic treatment. Blocking of dopamine receptors in the nigrostriatal pathway probably causes these unwanted parkinsonian symptoms. Clozapine and risperidone exhibit a low incidence of these symptoms. 

Most of the neurological disorders associated with the neuroleptics fall into the category of extrapyramidal reactions or extrapyramidal symptoms, and are often designated EPS. The extrapyramidal system of the brain is an extensive, complex network that moderates and adjusts motor... 

Palmer et al. (1999) focused on extrapyramidal symptoms (EPS) rather than TD and found that severity of EPS correlated with the severity of neuropsychological deficits, especially in the areas of learning and motor skills. Krausz et al. (1999) found a similar correlation between EPS and cognitive deficits on a self-rating scale. They believed the deficits were sufficient to cause potential difficulty with insight and everyday life skills. 

The primary treatment for schizophrenia involves use of antipsychotic medications. These are classified as typical or first generation, and atypical. The atypical antipsycho tics differ from the typical in having relatively less extrapyramidal side effects, such as rigidity, dystonia (muscle spasm), akathi-sia (motor restlessness), and pseudo-Parkinsonian symptoms. 

Basal ganglia Controls aspects of motor behavior Neuronal pathways connecting limbic system and prefrontal lobes Parkinson s disease, antipsychotic medication side effects (extrapyramidal symptoms (EPS)) Obsessive-compulsive disorder... 

In workers with chronic inhalation exposure, iron deficiency and liver cirrhosis are commonly observed. Chronic inhalation exposure also affects the CNS, resulting in Parkinsonian-like symptoms. Mental aberrations are also observed. The psychiatric disturbance has been called manganese madness . Symptoms include confusion, unusual behavior, and sometimes hallucinations. Apathy, difficulty with speech, and loss of balance are most common. Other symptoms include difficulty with fine motor movement, anxiety, and pain. Manganese intoxication can result in a syndrome of parkinsonism and dystonia. If these extrapyramidal findings are present, they are likely to be irreversible... 

Parkinsonism (Parkinson s disease) is a chronic neurologic disorder affecting balance and motion at the extrapyramidal motor tract. Five major symptoms of Parkinsonism are ... 

Paradoxical Reaction (particularly in children) manifested as excitation, nervousness, tremors, hyperactive reflexes, convulsions. CNS depression has occurred in infants and young children (respiratory depression, sleep apnea, SIDS). Long-term therapy may produce extrapyramidal symptoms noted as dystonia (abnormal movements), pronounced motor restlessness (most frequently occurs in children), and parkinsonian symptoms (esp. noted in elderly). Blood dyscrasias, particularly agranulocytosis, have occurred. 

Most patients who returned to society were able to function moderately well, but if they stopped their medication their condition deteriorated. Also, CPZ and compounds related to this phenothiazine series produced motoric side effects, including extrapyramidal side effects (EPS) that resemble Parkinson s disease. These symptoms could be severe and developed in up to 90% of patients on typical antipsychotic drugs. This condition often progressed to irreversible tardive dyskinesias, involuntary movements of the limbs and facial muscles that resemble the symptoms of Huntington s disease. In addition, such typical antipsychotics, although they were effective in treating the positive or florid symptoms of schizophrenia, did not ameliorate the negative symptoms of the disease. 

Extrapyramidal symptoms, akathisia, dystonia, tardive dyskinesia, drowsiness, headache, dry mouth, orthostatic hypotension Agitation, dizziness, nervousness, akathisia, constipation, fever, weight gain Hypotension, postural hypotension, tardive dyskinesia, photophobia, urticaria, nasal congestion, dry mouth, akathisia, dystonia, pseudo parkin son ism, behavioral changes, headache, photosensitivity Parkinson-like symptoms, motor restlessness, dystonia, oculogyric aisis, tardive dyskinesia, dry mouth, diarrhea, headache, rash, drowsiness... 

Thirty-seven tobacco workers from Brazil exposed to OP insecticides were clinically evaluated after a 3-momh application season, and some (25/37) were. subsequently evaluated 3 months after the cessation of pesticide use (Salvi et ai, 2003). At the time of the first evaluation, all subjects had been exposed to OP pesticides within 24 hr. None (0/37) had a history of acute intoxication within the past year. Significant extrapyramidal signs and symptoms were present in 12 patients. Although extrapyramidal signs improved during the no-exposure period, 10 patients still exhibited some motor difficulties after removal from pesticide exposure. 

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