This Study demonstrates that Progressive Multifocal Leukoencephalopathy (PML) is an unrecognized condition in sub-Saharan Africa, with a male to female ratio 4:2. Clinically, cognitive impairments, motor deficits, neurosensory symptoms, and cerebellar impairment predominated. Underlying pathologies leading to severe immunosuppression included HIV (3 cases), leprosy (1 case), systemic lupus erythematosus (1 case), and African trypanosomiasis (1 case). CSF PCR testing for J.C. virus was positive in all patients. Magnetic resonance imaging aided au diagnosis revealing large and multiple areas of hypointense signal in T1 and hyperintense signal in T2 and Flair in the white matter for all patients. except the lupus case. EEG findings indicated nonspecific bioelectrical disturbances characterized by generalized slowing down, with two patients (Patients 1 and 5) showing epileptic seizures, characterized by delta and theta rhythms with abnormal peak waveforms indicative of paroxysmal epileptic activity.