unesystem play a complex role, either protective or toxic, in ALSpathogenesis [1–3]. In particular, compelling evidence indicate thatincreased blood level of natural killer (NK) and NK-T cells may contributeto the disease development and progression [2,3].Here, we report on a patient with an aggressive Motor NeuronDisease (MND) associated with NK/NK-T cells leukaemia.1. Case reportA 79-year-old man presented with several months-history of aprogressive atrophy and weakness of the upper limbs, which quicklyspread to the lower limbs. Onset was subtle and apparently occurred inthe month of July (the specific date is not shown for privacy), when thepatient noticed a mild weakness in the proximal muscles of the rightarm. From July through August, the patient's global functioning washowever roughly normal. However, between September and earlyOctober the patient experienced a rapid worsening, with a severeweakness of the shoulder girdle, of the right arm and in both legs. Hewas referred to our ALS Center for evaluation. The neurological examinationdocumented marked muscle atrophy of the shoulder girdle,the right arm and both lower limbs, with bilateral foot drop. Deeptendon reflexes were absent, with the exception of the left arm. Bulbarfunctions were normal. Needle EMG showed widespread polyphasicMUP and fibrillation potentials, with normal sensory and motor conductionvelocities and no conduction blocks. Sensory and motor nervesamplitudes in the upper limbs were within the normal range. A brainand cervical MRI was within normal range. Extensive biochemical andimmunological work-up, including CSF, blood cell count, a large antibodybattery which included antibodies to anti-Hu, anti-Ri, anti-Yo, andanti-gangliosides were negative. Serum creatine phosphokinase levelwas mildly increased. A diagnosis of a very rapidly progressing lowermotor neuron disease (MND) was made, with an ALSFRS-R score of 18/48 and a ΔFS  of 10 (Fig. 1A).Although the clinical features of the patient did not fit with a formaldiagnosis of ALS, a genetic testing for the major ALS related genes(C9orf72, FUS, TARDBP, SOD1, and Angiogenin) was performed, whichgave negative results. In the middle of November 2016, a follow-upblood test showed a marked increase of WBC (i.e., 76,050/μL), with ahigh prevalence of lymphocytes.He was then admitted to the Hematology Unit in our Hospital. Bloodcytofluorimetric analysis and a bone marrow biopsy showed a markedinfiltration by immature NK and NK-T cells (Fig. 1B). A new CSF analysiswas performed, which showed increased proteins and 360/μL WBC, ofwhich about 70% were NK/NK-T cells. A diagnosis of NK/NK-T cell leukaemiawas made. A systemic chemotherapy according to Hyper-CVADschema was started (i.e., High Dose Dexamethasone; HyperfractionatedCyclophosphamide; Oncovine and Doxorubicine), along with repeatedintrathecal injections with Methotrexate, Ara-C and Dexamethasone.In the following weeks, the patient showed a transient improvementin muscle strength and function; a ALSFRS-R evaluation, made inDecember 2016, gave a score of 27/48, with a ΔFS dropping to 4.2(Fig. 1A). Unfortunately, the general health status deteriorated overtime, and in late December, the patient was referred to a Hospice,where a few weeks later he peacefully passed away.2. DiscussionWe have described an aggressive lower MND, which might beparaneoplastic, associated with an NK-T leukaemia. A paraneoplasticassociation between either lower MND and lymphoma or the upperpredominant MND and breast cancer has been reported [5–7].The presence of a high number of NK/NK-T cells
|Numero di pagine||2|
|Rivista||Journal of the Neurological Sciences|
|Stato di pubblicazione||Published - 2019|
All Science Journal Classification (ASJC) codes
- Clinical Neurology
La Bella, V., Spataro, R., Spataro, R., Iannitto, E., & Cuffaro, L. (2019). A rapidly progressive motor neuron disease associated to a natural killer cells leukaemia. Journal of the Neurological Sciences, 398, 117-118.