Chew et al. 1 studied the long-term natural history of Unverricht-Lundborg disease (ULD, progressive myoclonic epilepsy of Unverricht-Lundborg type, EPM1, OMIM #254800) in 8 patients with mutations in the cystatin B gene (CSTB). 1 Working in the area of Southern Sweden where Herman Lundborg (1868-1953) described this disorder that now bears his name, I recently read in his publications. [2][3][4] From 1898 to 1910, Lundborg compiled information on 17 patients afflicted by this condition. They all belonged to one extensive kindred, the ''Lister'' family.
While Chew et al. reported dystonia as a new clinical feature of EPM1, 1 it struck me that Lundborg described symmetrical tremor and marked rigidity. Lundborg distinguished three stages of the disorder: Beginning in childhood or early adolescence, nocturnal attacks with involuntary symmetric muscle twitches occurred (stage 1). Patients were awake and conscious during the attacks, which often were painful, caused anxiety, and reminded Lundborg of clonic, tonic-clonic, or tetanic seizures. A few years later, diurnal tremor, myokymia, and myoclonic or dystonic muscle contractions appeared, marking stage 2. Typically, the contractions initially affected the upper extremities symmetrically, and subsequently involved lower extremities, head, and neck, and finally, all muscles under voluntary control. Reminding of startle responses, tactile and auditory stimuli elicited these involuntary muscle contractions. Psychological stress aggravated them. Symptom severity fluctuated markedly from day to day. Gradually, increased muscle tone was noted in the interval between attacks. Several years to some decades later, further progression lead to stage 3 symptoms: As the nocturnal attacks disappeared completely, daytime muscle contractions became more and more pronounced. Regularly, marked generalized rigidity developed, leaving some patients utterly stiffened in certain poses, incapable of any voluntary movements. Lundborg noted that the clinical picture of some of his patients in the terminal phase reminded him of paralysis agitans (Parkinson's disease). 2 In contrast, tremor and rigidity are not mentioned in the other historical description of EPM1 by Unverricht, 5,6 or in patients with PME and CSTB-mutations. 1 Neither are these symptoms included in the 1990 diagnostic criteria for progressive myoclonic epilepsy of Unverricht-Lundborg type according to the Marseille consensus group 7 nor in Chew's case series. 1 Chew mentions rapidly progressing dementia and other psychiatric symptoms such as depression, emotional lability,