Table 2 -.
Secondary parkinsonisms
| Etiology | Mechanism | Differential clinical features vs. PD | Diagnosis | Therapy |
|---|---|---|---|---|
| Drug-induced * | Interference with DA-signaling | Often symmetric, perioral tremor, co-existent tardive syndromes. | Consistent history of exposure. Normal DAT- SPECT |
Discontinue the offending drug. Temporary use of anti-PD drugs |
| Vascular | Disruption of striato-pallido-thalamo-cortical motor network | Acute or subacute onset (not obligatory). Frequently presenting with gait disorder (lower body parkinsonism) | Strategic infarcts and subcortical microvascular lesions on MRI, normal DAT-SPECT (not obligatory) | Trial of L-Dopa Physiotherapy, occupational therapy |
| Toxic (Co, Mn) | Basal ganglia lesions (putamen, pallidum) | Symmetric parkinsonism, co-existent dystonia, severe dysarthria, ‘cock-gait’ (Mn) | History of exposure, MRI findings | Trial of L-Dopa. Physiotherapy, speech therapy, occupational therapy |
| Infectious | Basal ganglia abscesses or granuloma (toxoplasmosis, cryptococcosis; tuberculosis); encephalitic (HIV, CJD,PML) or postencephalitic basal ganglia involvement | Additional movement disorders and other neurological signs common | Medical history, systemic signs, MRI findings, CSF analysis, specific serologies. | Treatment of underlying conditions. Trial of L-Dopa |
| Autoimmune | Antineuronal antibodies affecting basal ganglia motor circuits (e.g., D2R-, DPPX, NMDA-, IGLON-5, & Ma2/Ta-AB’s) | Additional movement disorders and other neurological signs common | Antibody detection. Search for associated neoplasms |
Immunotherapy (IVIG, plasmapheresis, immunosuppressants), treatment of associated tumor |
| Neoplastic | Invasion or indirect compressive effects (frontal meningioma) of basal ganglia circuitry | Additional focal neurological signs | MRI | Treatment of underlying conditions. Trial of L-Dopa |
| Metabolic | Basal ganglia involvement (e.g., Wilson’s disease, non-ketotic hyperglycemia, extrapontine myelinolysis, calcium dyshomeostasis, hypermagnesemia in liver disease, iron deposition in NBIA’s) | Additional movement disorders and other neurological, psychiatric and systemic signs common | Specific laboratory and imaging studies | Treatment of underlying conditions. Trial of L-Dopa |
| NPH | Compromised prefrontal motor connectivity | Small stepped & broad-based gait disorder with freezing, no rest tremor or upper limb involvement (‘lower body parkinsonism’) | Neuroimaging (brain CT or MRI) | CSF drainage (repeated LP, ventricular shunting) |
| Functional | Multifactorial, includes psychiatric comorbidity and impaired self-agency | Abrupt onset, spontaneous fluctuation, effortful demonstrative slowness, tremor with frequency variation and entrainment, no response to levodopa | History of psychiatric comorbidity, incongruent clinical presentation, remission with behavioral or psychotherapy | Counseling. Cognitive behavioral psychotherapy |
Most common offending drugs: DA receptor blockers including first generation (phenothiazines and butyrophenones) and second generation (e.g., olanzapine, risperidone, sulpiride, aripiprazole) antipsychotics as well as antiemetics ( metoclopramide, prochlorperazine and triflupromazine); DA depleting drugs (tetrabenazine or reserpine); Ca- antagonists (flunarizine, cinnarizine and verapamil); antiepileptics (valproate, carbamazepine or lamotrigine); antidepressants (SSRIs, combined noradrenergic -serotonergic reuptake inhibitors and antimuscarinics).
Abbreviations: DA Dopamine; DAT: dopamine transporter; SPECT: Single-photon emission computed tomography; CO Copper; MN Manganese; MRI magnetic resonance imaging; IVIG: intravenous immunoglobulin immunoglobulins; NBIA: neurodegeneration with brain iron accumulation; CT: computed tomography; NPH: normal pressure hydrocephalus; LP: lumbar puncture.