Introduction to movement disorders and parkinsonism Domina Petric, MD

Tremor I.

Tremor Tremor consists of a rhythmic oscillatory movement around a joint. It is best characterized by its relation to activity. Tremor at rest is characteristic of parkinsonism, when it is often associated with rigidity and an impairment of voluntary activity.

Tremor Tremor may occur during maintenance of sustained posture (postural tremor) or during movement (intention tremor). A conspicious postural tremor is the cardinal feature of benign essential or familial tremor.

Tremor Intention tremor occurs in patients with a lesion of the brainstem or cerebellum, especially when the superior cerebellar peduncle is involved. It may also occur as a manifestation of toxicity from alcohol or certain other drugs.

Chorea II.

Chorea Chorea consists of irregular, unpredictable, involuntary muscle jerks that occur in different parts of the body and impair voluntary activity. The proximal muscles of the limbs are usually most severely affected. Abnormal movements of proximal muscles are particularly violent: BALLISMUS.

Chorea Chorea may be hereditary or may occur as a complication of number of general medical disorders and of theraphy with certain drugs.

Athetosis, dystonia III.

Athetosis www.5minuteconsult.com

Dystonia Sites.google.com

Athetosis, dystonia Acute complication of certain drugs Perinatal brain damage with focal or generalized cerebral lesions Acute complication of certain drugs Accompaniment of diverse neurologic disorders Isolated inherited phenomenon of uncertain cause (idiopathic torsion dystonia, dystonia musculorum deformans)

Tics IV.

Tics Tics are sudden coordinated abnormal movements that tend to occur repetitively, particularly about the face and head, especially in children. Tics can be suppressed voluntarily for short periods of time. Common tics include repetitive sniffing or shoulder shruging.

Tics Tics may be single or multiple and transient or chronic. Gilles de la Tourette´s syndrome is characterized by chronic mutliple tics.

Basal ganglia Many of the movement disorders have been attributed to disturbance of the basal ganglia. The basic circuitry of the basal ganglia involves three interacting neuronal loops: cortex thalamus basal ganglia

Parkinsonism V.

Parkinsonism It is characterized by a combination of rigidity, bradykinesia, tremor and postural instability. It is usually idiopathic: Parkinson´s disease or paralysis agitans. Cognitive decline occurs in many patients as the disease advances.

Nonmotor symptoms Personality changes Affective disorders: anxiety, depression Abnormalities of autonomic function: sphincter or sexual functions, choking, sweating abnormalities, disturbances of blood pressure regulation Sleep disorders Sensory complaints, pain

Parkinsonism The disease is generally progressive, leading to increasing disability unless effective treatment is provided.

Pathogenesis impaired degradation of protiens intracellular protein accumulation and aggregation oxidative stress mitochondrial damage inflammatory cascades apoptosis

Pathogenesis Recognized genetic abnormalities accout for 10-15% of cases. Mutations of the α-synuclein gene at 4q21 or duplication/triplication of the normal synuclein gene: synucleinopathy.

Pathogenesis Mutations of the leucine-rich repeat kinase 2 (LRRK2) gene at 12cen, and the UCHL1 gene may also cause autosomal dominant parkinsonism. Mutations in the parkin gene (6q25.2-q27) cause early-onset, autosomal recessive, familial parkinsonism or sporadic juvenil-onset parkinsonism.

Pathogenesis Cigarette smoking, coffee, anti-inflammatory drug use and high serum uric acid levels may be protective. The incidence of the Parkinson´s disease is increased in those working in teaching, health care, farming and in those with lead or manganase exposure and with vitamin D deficiency.

Lewy bodies Intracellular inclusion bodies containing α-synuclein.

Braak stages: Lewy bodies Stage I Stage III Stage V and VI Olfactory nucleus and lower brainstem Substantia nigra: motor features develop Neocortex 1 2 3 4 5, 6 Stage II Stage IV Higher brainstem The mesocortex and thalamus

Stage I The disease begins in structures of the lower brainstem and the olfactory system. In particular, the dorsal motor nucleus of the vagus nerve in the medulla oblongata and anterior olfactory nucleus are affected. Lewy neurites, thread-like alpha-synuclein aggregates, are more prevalent than globular Lewy bodies in this stage.

Stage II It is characterized by additional lesions in the raphe nuclei and gigantocellular reticular nucleus of the medulla oblongata. The disease then moves up the brainstem, traveling from the medullary structures to the locus ceruleus in the pontine tegmentum. Lewy neurites outnumber Lewy bodies.

Stage III At the beginning of stage III, the disease has entered the substantia nigra and Lewy body lesions begin to form in the pars compacta.  The latter half of this stage involves disease progression into the basal nucleus of Meynert, a cluster of acetylcholine-rich neurons in the basal forebrain.  Further, structures affected in stages I and II begin to develop more Lewy bodies.

Stage IV It is characterized by severe dopaminergic cell destruction in the pars compacta. There is also mesocortex and allocortex involvement. The neocortex remains unaffected. In particular, pathology can be observed in the amygdala and in the subnuclei of the thalamus. There is significant damage done to the anterior olfactory nucleus.

Stage V The disease has started to invade the neocortex and spreads into the structures of the temporal, parietal, and frontal lobes.  Cell death can be observed in the substantia nigra, the dorsal motor nucleus of the vagus nerve, the gigantocellular reticular nucleus and the locus ceruleus.

Stage VI The disease has fully invaded the neocortex, affecting the motor and sensory areas in the brain.

Wikimedia Commons Braak stage V, VI: neocortex Emotional and cognitive disturbances Braak stage IV: mesocortex, thalamus Sleep disturbances Motor disturbances Braak stage III: substantia nigra Braak stage II: higher brain stem Braak stage I: olfactory nucleus, lower brainstem Olfactory and autonomic disturbances Wikimedia Commons

Pathogenesis The normally high concentration of dopamine in the basal ganglia of the brain is reduced in parkinsonism. Levodopa and dopamine agonists alleviate many of the motor features. Restoration of the normal balance of cholinergic and dopaminergic influences on the basal ganglia: antimuscarinic drugs.

Pathogenesis In idiopathic parkinsonism, dopaminergic neurons in the substantia nigra that normally inhibit the output of GABAergic cells in the corpus striatum are lost. Drugs that induce parkinsonian syndromes are dopamine receptor antagonists (antipsychotic agents) or lead to the destruction of the dopaminergic nigrostriatal neurons (MPTP).

Norepinephrine is also depleted in the brain in parkinsonism. Pathogenesis Norepinephrine is also depleted in the brain in parkinsonism.

Literature Katzung, Masters, Trevor. Basic and clinical pharmacology. www.5minuteconsult.com Wikipedia.org