Clinical profile of genetically confirmed Spinal Muscular Atrophy (SMA) Among Filipino children less than 18 years old

@#Spinal muscular atrophy (SMA) is the most common inherited lethal disease in children. Confirmatory diagnosis is based on molecular genetic testing of survival motor neuron (SMN) genes. We aimed to describe the phenotypic presentation of Filipino infants and children with SMA based on the copy number analysis of SMN genes. Medical records of 17 Filipino children were reviewed from January 2017 to December 2019. De-identified clinical data fulfilled the diagnostic criteria defined by the International SMA Consortium. Among Filipino children, the predominant SMA type by copy number was type I having two copies of SMN2 gene. The clinical severity based on symptom onset and highest functional motor capacity attained correlated with SMN2 copy number congruent with existing data. A significant time lag between symptom onset to confirmation of genetic diagnosis was noted. Nine out of the 17 (52%) children did not have a family history of the disease, raising the possibility of mutation carriers in these families since the incidence of de novo mutations in literature is about 2%. These data offered the first epidemiological pattern of genetically confirmed SMA among Filipino children; provided additional information for genetic counselling; and an avenue to consider pre-symptomatic newborn screening and carrier testing that would change proactive measures and opportunities for therapy. These measures unavoidably will decrease the incidence and prevalence of disease in the future.

Duchenne muscular dystrophy in a Filipino boy reaching adulthood, and nine years into oral corticosteroids: A case report

Rationale@#Duchenne muscular dystrophy (DMD) is a disease that primarily manifests in the early stages of life and progressively affects muscle strength resulting in quadriparesis and ultimately resulting in premature death secondary to cardiac or respiratory failure. DMD is the most common x-linked genetic disorder in children that is because of an alteration of a protein called “dystrophin” which is responsible for strengthening muscle fibers and protecting them from injury as muscles contract and relax. @*Objective@#To highlight the case of a 19-year-old male who was diagnosed with DMD at 8 years of age and treated with oral corticosteroid and rehabilitation. @*Case@#We present the case of a 19-year-old male who developed difficulty climbing stairs and was diagnosed with DMD at 8 years old with the use of clinical exome sequencing. Corticosteroid therapy was initiated and rehabilitation perpetuated which dramatically improved his life expectancy. @*Discussion and Summary@#Clinical exome sequencing was employed on our patient to confirm the diagnosis of DMD from other neuromuscular and neurodegenerative diseases. Most cases of DMD succumb to cardiopulmonary arrest before reaching adulthood; however, this case exemplifies DMD from other cases since our patient was able to prolong his life with continuation of oral corticosteroid and rehabilitation and in the absence of extensive life support.

A basic review of Sarcopenia Diagnosis

@#Associated with aging, sarcopenia is characterized by a decline in skeletal muscle mass, muscle strength and physical performance, eventually resulting in reduced physical capability, disability, poor quality of life, mortality in older people and high health care expenditure. The prevalence varies significantly by population characteristics, disease status, diagnostic criteria and measurement tools. It is essential to achieve an accurate diagnosis of sarcopenia for the management plan to be effective. This review briefly discusses the essential steps in diagnosing sarcopenia: Find – Assess – Confirm - Severity.

Botulinum neurotoxin a for hand tremors in Parkinson’s disease: A meta-analytic study

Background@#Resting tremor is a prominent cardinal motor symptom of Parkinson’s disease (PD). In some cases, the tremor may be refractory to dopaminergic and anticholinergic treatment. Multiple studies were previously done to evaluate the effectiveness of Botulinum Neurotoxin A (BoNT/A) with essential tremors and dystonia, but data regarding its use on tremors of PD is still lacking. @*Objective@#This meta-analytic study aims to determine the effectiveness of BoNT/A in treating tremors of patients with PD. @*Data Sources@#Data Sources: Researches were searched at PubMed, ScienceDirect and EBSCO Host. @*Review Methods@#Articles on the effect of BoNT/A on PD hand tremors were searched. Studies and data pertaining to non-PD tremors like essential tremors excluded in the analysis due to difference in pathophysiology. Standardized mean difference was used as the effect measure and was computed with Review Manager version 5.4 software. @*Results@#Three open label studies were used for final analysis in this study. Studies included are those pertaining to tremors due to PD. Pooled estimates showed a significant change in decreasing tremor score after BoNT/A injection. @*Conclusion@#Botulinum Toxin A injections can be used to manage PD tremors effectively.

Fork in the road: Pick research and publication

@#I see clinicians often and when time is kind, a conversation about research ensues. There is always interest but to actually engage in research, many shake their heads and sigh “no time.” I wonder about lost opportunities to learn and study diseases when clinicians are not inclined to or not supported in research. At every stage of medical education, training, and professional practice whether in academia or in clinic or hospital, physicians inevitably encounter a fork in the road. The paths of clinician and/or academician are large lanes in the highway, yet at a junction, the highway becomes two roads, one to remain as clinician or academicians and the other to pursue research and publication. As well-known, many choose to remain in clinic or in classroom.

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin abnormalities (POEMS) syndrome in a Filipino nurse returning to work following bortezomib treatment: A case report

@#<p style="text-align: justify;" data-mce-style="text-align: justify;"><span style="color: #525a63; font-family: Lato, sans-serif; font-size: 16px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: #ffffff; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial; display: inline !important; float: none;" data-mce-style="color: #525a63; font-family: Lato, sans-serif; font-size: 16px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: #ffffff; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial; display: inline !important; float: none;">POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) also known as Crow-Fukase syndrome or Takatsuki syndrome is a rare and disabling paraneoplastic syndrome that frequently occurs in the fifth or sixth decade of life without a known standard first-line therapy. A 34-year-old Filipino male nurse, who presented with gradually progressive distal lower extremity weakness and sharp shooting pain in bilateral legs accompanied by mild joint effusion on the left knee, hypertrichosis, bilateral conjunctival injection, and gynecomastia underwent extensive workup and was diagnosed with POEMS syndrome. Complete blood count revealed erythrocytosis and thrombocytosis with elevated serum VEGF (vascular endothelial growth factor) and elevated monoclonal serum free lambda light chains. The electrophysiologic studies revealed chronic demyelinating sensorimotor polyneuropathy while bone marrow core biopsy and bone marrow aspirate smear immunohistochemical staining showed it to be positive for lambda and CD138. He had an initial unsuccessful treatment course with melphalan and prednisone. Hence, bortezomib and dexamethasone were given which gave significant improvement in symptoms from the overall neuropathy limitation score of 5 to 1.</span></p>

Viewpoint : Physician as a clinician, researcher, and academician

The daily work life of physicians who function as clinicians, researchers, and academicians is focused on improving public health and patient outcomes in three usually compartmentalized settings: clinics, classrooms, and centers for research. In these settings, physicians are addressing patients' medical concerns based on evidence, and at the same time, considering if new information could lead to research and discovery for better patient outcomes. The physician then proceeds to mentor, teach, and train medical students in quality evidence-based clinical practice and the conduct of scientific research. The importance of operationally blending these three disciplines with research as a common thread is not only a big challenge for these physicians but also an opportunity to innovate for better public health.

Constrictive entrapment neuropathies of a limb secondary to restraint strapping: A case report

@#<p style="text-align: justify;"><strong>Rationale:</strong> Entrapment neuropathies are peripheral nerve disorders at specific anatomical locations. They may be caused by trauma in a manner of sprains or bone fracture, but it is often caused by repetitive insults or compression of nerves as they travel through a narrow anatomic space. Pregnancy and pre-existing comorbidities such as diabetes, obesity, cancer, or autoimmune diseases may also cause nerve entrapment.</p><p style="text-align: justify;"><strong>Objective:</strong> To highlight the case of a 52-yearold female developing right foot dysesthesia and weakness after continuous restraint strapping from her previous hospitalization.</p><p style="text-align: justify;"><strong>Case:</strong> Here we have the case of a 52-year-old Filipino female consulted because of right foot dysesthesia, allodynia, and mild weakness. She had a history of bipolar disorder and recent onset of acute psychosis and overdosing with her irregularly taken maintenance olanzapine tablets. She was put on restraint strapping of the right lower limb in her one-week hospital stay. This resulted in developing restraint marks on her right ankle accompanied by difficulty walking on heels and toes, spontaneous dysesthesia, and touch allodynia of her entire right foot. An electrodiagnosis yielded right lower limb focal neuropathies involving the right fibular nerve, right tibial nerve, right superficial fibular, and right sural nerves. The prescribed amitriptyline and gabapentin for 6 months led to gradual improvement of neuropathic pain.</p><p style="text-align: justify;"><strong>Discussion and Summary:</strong> Our case exemplifies focal limb neuropathies from entrapment due to restraint strapping. Electrodiagnostic confirmation of neuropathies of the same limb sensory and motor nerves was mandated to corroborate clinical neuropathic pain and after ruling out other causes of entrapment neuropathies. Prolonged use of neuropathic pain medications were needed to attain relief in this present case. Restrictive strapping is an iatrogenic cause of entrapment neuropathy that is preventable, had there been proper medical attention applied.</p>

Viewpoint: Physician as a Clinician, Researcher, and Academician

@#The daily work life of physicians who function as clinicians, researchers, and academicians is focused on improving public health and patient outcomes in three usually compartmentalized settings: clinics, classrooms, and centers for research. In these settings, physicians are addressing patients’ medical concerns based on evidence, and at the same time, considering if new information could lead to research and discovery for better patient outcomes. The physician then proceeds to mentor, teach, and train medical students in quality evidence-based clinical practice and the conduct of scientific research. The importance of operationally blending these three disciplines with research as a common thread is not only a big challenge for these physicians but also an opportunity to innovate for better public health.

painDETECT Questionnaire Filipino version: Transcultural adaptation and validation in two widely spoken regional languages (Tagalog and Cebuano)

@#Background & Objective: Chronic pain impacts the quality of life of patients, with neuropathic pain causing profound negative sequelae. Assessment of pain whether nociceptive or neuropathic is important to provide appropriate treatment. The objective of this study is to translate and validate the pain-DETECT Questionnaire (PDQ) to two widely spoken regional languages in Filipino. Methods: The PDQ, a self-administered questionnaire, was translated from English into the Filipino version, painDETECT Tagalog (PDQ-Tag) and painDETECT Cebuano (PDQ-Ceb). One hundred Filipino patients suffering from pain for at least three months were recruited in the out-patient clinics of a hospital and completed the questionnaire. The investigators, blinded to the subjects PDQ-Tag and PDQ-Ceb scores, examined the subjects using the standard clinical and neurological examination. The PDQ-Tag and PDQ-Ceb, scores were validated. Both questionnaires were administered to the same patient twice, two days apart by the same investigator. Results: Seventy subjects completed the (PDQ-Tag) and thirty subjects the (PDQ-Ceb). The sensitivity and specificity of PDQ-Tag were both 80% for an upper limit cut-off value of ≥ 17. The sensitivity and specificity of PDQ-Ceb were 62.5% and 80% respectively, for an upper limit cut-off value ≥ 18.0. Both questionnaires were reliable [Cronbach’s alpha coefficient: 0.78 (PDQ-Tag) and 0.70 (PDQ-Ceb), good test-retest stability with intra-class correlation coefficient: 0.93 for PDQ-Tag and 0.99 for PDQ-Ceb]. Cohen’s kappa were 0.64 and 0.61 for PDQ-Ceb and PDQ-Tag respectively, with P value<0.001 indicating a significant agreement on the assessment of neuropathic pain. Conclusion: PDQ-Tag and PDQ-Ceb are reliable and valid self-administered screening tools to detect neuropathic pain among Filipinos.

Acute Ischemic Stroke in a Filipino with Parkinsonian Fahr’s Disease: A Case Report

@#Fahr’s Disease (FD) is a rare neurodegenerative disorder of uncertain etiology characterized by abnormal intracranial calcium deposition in the basal ganglia. It initially presents in the 4th to 6th decade of life with diverse neuropsychiatric manifestations. The correlation between vascular calcifi cation and coronary artery disease had been studied extensively, but its correlation with cerebrovascular disease remains elusive. Vascular calcifi cation is thus an important risk factor for coronary artery disease. It was also postulated that a similar risk for cerebrovascular disease may be attributable to intracranial vascular calcifi cation. We present the case of a 46-year-old male with progressive affective and cognitive disturbances, parkinsonism and ataxia. Eight years after initial presentation, he developed an acute ischemic infarct in the background of diffuse intracranial calcifi cation characteristic of FD, confi rmed by neuroimaging (Figure 1). While a number of cases FD with associated stroke or stroke-like symptoms have been reported, we are unaware of such occurrence in a Filipino. A pathologic model linking intracranial vascular calcifi cation in FD with cerebrovascular disease and ischemic stroke has been proposed, and warrants further investigation.