The presenting symptoms of Lafora Disease: An electroclinical and genetic study in five Apulian (Southern Italy) families.

PURPOSE: To elucidate the presenting symptoms of Lafora Disease (LD) to differentiate it from Juvenile Myoclonic Epilepsy (JME). METHODS: We collected and evaluated the early electroclinical data of 5 unrelated Apulian (Southern Italy) LD families, 30 LD patients selected from the literature, and 30 Apulian JME patients. RESULTS: The Apulian LD patients presented with generalised tonic-clonic and focal visual seizures, followed by myoclonic seizures and action-postural myoclonus. In these patients, EEG background slowing and occipital epileptiform abnormalities were significantly more evident than in the other groups. Genetic analysis revealed the presence of mutations in the EPM2A gene in 4 families, and in the NHLRC1 gene in the remaining family. In detail, we identified 2 different point mutations in EPM2A and only 1 in NHLRC1, and expanded the molecular spectrum of the EPM2A gene mutations reporting for the first time a patient carrier of the c.243_246del genetic variant. In the previously reported LD cases, generalised tonic-clonic and focal visual seizures and myoclonus were the most frequent symptoms, as confirmed by the first EEGs showing occipital or diffuse epileptiform abnormalities with photosensitivity in the background activity slowing. In the Apulian JME patients, myoclonus appeared earlier, usually at awakening, with diffuse epileptiform abnormalities during sleep and photosensitivity in the normal background activity. The diagnosis of JME was established much earlier than the LD one. During evolution, unlike JME patients, LD patients showed a significant resistance to drugs. CONCLUSIONS: Tonic-clonic and focal visual seizures followed by myoclonic seizures and action-postural myoclonus together with EEG background slowing with diffuse and occipital epileptiform abnormalities suggest a diagnosis of LD. An early molecular confirmation allows a better diagnosis, counselling and management of affected patients and their families, and it may be useful to improve the patients' quality of life using, when possible, emerging personalized treatments that may slow the evolution of the disease.

What do spinal cord injury patients think of their improvement? A study of the minimal clinically important difference of the Spinal Cord Independence Measure III.

BACKGROUND: The Spinal Cord Independence Measure (SCIM III) is a scale of independence in the activities of daily life, specifically designed for spinal cord injury subjects. AIM: The aim of this study was to calculate the minimal clinically important difference (MCID) of the SCIM III according to distribution and anchor based approach. DESIGN: Prospective study. SETTING: Four Spinal Cord Units in Italy. POPULATION: Patients with acute/subacute spinal cord injury/lesion. METHODS: The scores of the total SCIM and of the four subscale was recorded at admission and discharge. Clinical significance was calculated according to anchor based methodology using a global rating of change questionnaire. The accuracy of MCID values in predicting a judgment of small improvement by the patients has been assessed by means of the area under the receiving operating curves (aROC). RESULTS: Total SCIM MCID values varied from 12 for patients with complete tetraplegia to 45.3 for those with incomplete thoracic lesions. The MCID of self-care varied from 3.3 to 8.5 and from 10 to 18 for respiration and sphincter management, depending on the level and severity of the lesion. With regard to mobility (room and toilet), the MCID varied from 1 to 3 and from 2.5 to 7.26 for mobility (indoors and outdoors). The aROC was between good and excellent for all these values. CONCLUSIONS: The results provide benchmarks for clinicians and researchers to interpret whether patients' change score on the SCIM III can be interpreted as true or clinically meaningful and to make clinical judgments about the patients' progress. CLINICAL REHABILITATION IMPACT: Our data could be useful for both clinicians and researchers. At the beginning of rehabilitation clinicians may have an idea of the minimal improvement of the patient (based on his neurological status) that could have an impact on patient's life. At the end of rehabilitation process, it is possible to control if the patient achieved an improvement that is true and significant. Researchers could also use these criteria to evaluate the clinical significance of an intervention by calculating the number of subjects in the treatment and control groups (or in two different treatment groups) who achieved a change calculated as the natural recovery plus the MCID.