History Of Multiple Sclerosis Research Articles

Article Review: Multiple Sclerosis

Neurology still puzzles about multiple sclerosis (MS). This comprehensive overview explores MS's history, epidemiology, etiology, clinical manifestations, diagnostic tools, and treatment options. From historical awareness to cutting-edge research, we traverse MS's complex world with a focus on the past and future. Genetics, environment, and migration interact to create geographic riddles in MS prevalence. MS's sensory and cognitive symptoms show its significant influence. Advanced imaging technology and diagnostic criteria enable accurate and quick identification. While transformational, disease-modifying treatments require a tailored approach. Advances have left crucial gaps, prompting researchers, physicians, and policymakers to continue. This in-depth investigation of MS combines historical and future perspectives to emphasize the urgency and possibility of solving this complicated neurological puzzle.

A case of acute invasive fungal sinusitis in an immunocompetent patient on glatiramer acetate therapy

Acute invasive fungal sinusitis (AIFS) is a rapidly progressing, life-threatening infection. The advent of immunomodulatory therapies has expanded the population susceptible to AIFS. In this case report, we describe a patient who defies the conventional profile of AIFS. This 70-year-old woman is immunocompetent and non-diabetic, with a history of multiple sclerosis (MS) and ongoing treatment with glatiramer acetate (GA), immunomodulator. She came to the emergency room due to acute vision changes, and images revealed an enhancing mass in the left pterygopalatine fossa. The diagnosis of AIFS was confirmed by biopsy in the operating room. Subsequently, anti-fungal therapies were initiated with a follow-up operative debridement. Follow-up magnetic resonance imaging (10 months since treatment) showed no progression of AIFS. GA was discontinued since the diagnosis, and MS has remained stable. Recognizing this unique group of atrisk patients is crucial, as early detection and treatment play a pivotal role in preventing significant morbidity and mortality.

Biotin induced biochemical hyperthyroidism: a case report and review of the literature

BackgroundBiotin is a commonly used supplement for hair, nail, and skin. Recent literature suggests that high-dose biotin therapy for neurological diseases like Multiple sclerosis can interfere with lab results that use biotin/streptavidin immunoassay, called biotin interference. Biotin interference can affect thyroid lab results, giving biochemical hyperthyroidism.Case presentationOur patient, a 64-year-old white man with a known history of multiple sclerosis, presented with elevated free T3, free T4, and low TSH that resembled hyperthyroidism. He had no symptoms of hyperthyroidism except some fatigue and tachycardia on the first encounter. He was started on anti-thyroid medications. He was then re-evaluated since his lab results remained the same after two months of anti-thyroid medications. It was found that he was on biotin, 10000mcg/day, for his multiple sclerosis. Biotin was discontinued, and five days later his lab results returned to normal values.ConclusionThe lack of knowledge of biotin use by patients can lead to misdiagnosis of patients’ thyroid lab results and improper management. Awareness about biotin interference and abnormal thyroid lab values should be a priority among clinicians and the public. If the biotin is discontinued on time, such misdiagnosis can be avoided.

Neurosarcoidosis in an adult man with a family history of MS: A case report

Key clinical messageAccording to this report, a biopsy revealed a diagnosis of neurosarcoidosis in a patient with a history of MS. The development of the disease can be slowed down by early diagnosis and appropriate treatment.AbstractNeurosarcoidosis is a rare type of sarcoidosis that affects the central nervous system (CNS). Herein, we present a case of neurosarcoidosis with a history of multiple sclerosis (MS). Based on the pathological findings of the biopsy, a diagnosis of neurosarcoidosis was established. The administration of appropriate treatment at an early stage can assist in decelerating its progression.

Neurodegeneration with brain iron accumulation: a differential diagnosis of cerebral palsy

BackgroundBrain iron accumulation neurodegeneration (NBIA) comprises a group of rare diseases characterized by deposits of this metal in brain structures. It presents a great variability of progression, which can be fast enough to lead the patient to death in the first years of life, or slow enough to be confused with non-progressive diseases.Case presentationFemale, 19-year-old patient, cesarean delivery at 38 weeks of gestation. History of multiple sclerosis in a second-degree paternal aunt. Normal neuropsychomotor growth and development up to 11 months, when changes in gait began. After that, it got worse, with decreased muscle strength and falls, but it progressed so slowly that she was diagnosed with cerebral palsy, a non-progressive condition. At the age of 16, she underwent molecular analysis by exome sequencing, being diagnosed with the NBIA Phospholipase A2 (PLAN) variant. Currently doing physical therapy, hydrotherapy, occupational therapy and sertraline.ConclusionsThe report draws attention to the variability of the disease and the possibility of confusion with other diagnoses, which may delay proper management.

Focus or Neglect on Cognitive Impairment Following the History of Multiple Sclerosis

Cognitive disorders are now considered an integral part of the picture of multiple sclerosis. If we trace the history of the accounts of this disease, from the early descriptions by Jean-Martin Charcot, the first to provide systematic characteristics of multiple sclerosis, to present-day accounts, reports of cognitive disturbances have demonstrated an alternating trend. Cognitive disturbances were identified in the beginning, quite clearly for the times. Then, for a long time, they were considered infrequent or attributed to other factors. Finally, since the 1980s, cognitive disturbances have been the subject of increasingly in-depth studies, and are currently assumed to be a very important consequence of multiple sclerosis. In this work, the history of the description of cognitive disorders of multiple sclerosis will be retraced by analyzing the possible reasons for the differences in attention they have received over time. It emerged from the analysis that, as in the case of other pathologies, various factors have influenced how cognitive disorders have been taken into consideration. Some of these factors are inherent to the very nature of the cognitive impairments present in multiple sclerosis; others are linked to historical periods, or to the different ways of approaching the analysis of the phenomena caused by a disease. The reflections made on these topics should, among other things, increase our awareness of how scientific investigation is invariably placed in the historical context in which it is carried out.

Recurrent encephalopathy associated with pegylated beta-interferon treatment

A 62-year-old woman with a history of multiple sclerosis (MS) presented with recurrent episodes of confusion, dysarthria and gait difficulties. These episodes occurred about 3 days after administration of pegylated interferon-beta-1a (Plegridy®) and resolved spontaneously in around 4 days. The brain MRI scan, laboratory findings and cerebrospinal fluid analysis during these episodes were negative for other causes of encephalopathy. She discontinued treatment with interferon and was started on teriflunomide, experiencing no recurrence of symptoms. We believe that interferon was responsible for this patient's recurrent encephalopathic syndrome, possibly due to its effects on inflammatory cytokines and endothelial dysfunction.

Corneal Molluscum Contagiosum Masquerading as Ocular Surface Squamous Neoplasia

A 47-year-old woman with history of multiple sclerosis on ocrelizumab was referred for evaluation of leukoplakic placoid inferior limbal-corneal lesion of the left eye (A). Anterior-segment OCT demonstrated a well-circumscribed intraepithelial mass (B). The conjunctiva and eyelids were unremarkable. The lesion did not respond to topical interferon-alpha for presumed ocular surface squamous neoplasia, so the mass underwent excision. Histopathology revealed a thickened limbal-corneal epithelium with hypergranulosis (arrow), surface keratinization (asterisk), and molluscum contagiosum bodies (arrowheads) (C, hematoxylin-eosin, 400×). Further questioning disclosed a history of multiple self-limited eyelid margin nodules, suggestive of cutaneous molluscum contagiosum (Magnified version of Figure A-C is available online at www.aaojournal.org).

A Case Report of Three Guillain-Barré Syndrome During SARS-CoV-2 Pandemic: Promising Outcome in a Patient with History of Multiple Sclerosis

Neurologic complications in patients with coronavirus disease 19 (COVID-19) are common particularly in hospitalized patients. Guillain–Barré syndrome (GBS) is a rare complication of COVID-19. Most patients with GBS and COVID-19 presented with progressive, ascending limb weakness evolving over one to four days. There are some reported cases of GBS, mostly in form of case reports or case series, and also a comprehensive review on this topic. However, none of these cases experienced multiple sclerosis (MS) as an underlying disease. So, in this manuscript we reported three cases of COVID-19 induced GBS; one of them with history of MS and promising outcome after receiving five sessions of plasmapheresis and corticosteroid therapy.

BLUE FINGERS, EOSINOPHILIC LUNGS: ACUTE EOSINOPHILIC PNEUMONIA FOLLOWING COVID-19 INFECTION

BLUE FINGERS, EOSINOPHILIC LUNGS: ACUTE EOSINOPHILIC PNEUMONIA FOLLOWING COVID-19 INFECTION

Baclofen-Induced Coma Reversible by Dialysis in a Patient Affected by Acute Kidney Injury

Baclofen is commonly used to treat muscular spasticity and other conditions such as pain, alcohol withdrawal, and myoclonus. It is contraindicated in chronic kidney disease. As it is eliminated predominantly by the kidneys, acute kidney injury can lead to acute baclofen overdose with central nervous system affection due to drug accumulation. Currently, there is no consensus about the treatment of baclofen intoxication.A 67-year-old woman was admitted with altered mental status and vomiting. Initially, she was unresponsive/lethargic and kept the intermittent ability of nonverbal communication gradually sliding into a comatose state with apneas. Initial neurologic and radiologic examinations ruled out a structural lesion of the central nervous system. Laboratory data showed acute kidney injury and suspected urinary tract infection with extremely high inflammation parameters. The patient had a history of multiple sclerosis and received daily oral baclofen. Baclofen-induced coma secondary to baclofen overdose caused by renal insufficiency was suspected and renal dialysis started within 24 hours. Cystoscopy and implantation of a ureteric stent were necessary because of obstructive nephropathy. During hemodialysis, the patient’s mental status steadily improved. The patient woke up and was oriented and cooperative. Both clinical and laboratory data were widely normalized within days.Diagnosis of baclofen overdose can be challenging, but adequate supportive therapy, including hemodialysis, should be considered to reduce the length of comatose state and the risk of aspiration pneumonia.

Non-Compaction Cardiomyopathy and Multiple Sclerosis: Associated or Independent Diseases? A Case Report

Non-compaction cardiomyopathy (NCCM) is associated with neuromuscular disorders; however, there has been little investigation on its association with other neurological diseases, such as multiple sclerosis. We present the case of a 46-year-old woman with a history of multiple sclerosis who developed heart failure and was diagnosed with non-compaction cardiomyopathy.

General knowledge and Attitudes Toward Multiple Sclerosis: A Cross-Sectional Study

Introduction: Multiple sclerosis is an inflammatory and chronic disease of the central nervous system. Lack of knowledge about the disease and its symptoms may delay early diagnosis and control of the disease. The present study aimed to investigate the general knowledge and attitude towards multiple sclerosis in Isfahan.
 Methods: This was a cross-sectional (descriptive-analytical) study conducted in 2021 in Isfahan. A researcher-made questionnaire with 22 questions was created and distributed online through social networks. Data were analyzed using independent t-test and one-way analysis of variance with SPSS software (v.24).
 Results: A total number of 480 people participated in this study. The mean scores of knowledge and attitude were 4.77±1.86 and 54±6.24, respectively. T-test results indicated that there is a significant difference between participants' knowledge and attitude scores in terms of gender and history of multiple sclerosis in those around them. Analysis of variance results also showed that there is a significant difference in the mean scores of participants' knowledge and attitude according to their education level and job status. But there was no difference in the participants' attitudes toward multiple sclerosis and patients with multiple sclerosis according to their marital status.
 Conclusion: Based on the present study findings, participants' knowledge about multiple sclerosis was moderate. Therefore, Measures must be taken in order to increase the public awareness through the mass media and health centers. It can help to early diagnose and control of the disease and correcting the people's misconceptions about patients with multiple sclerosis.

A Case of Chronic Relapsing Inflammatory Optic Neuropathy

Chronic relapsing inflammatory optic neuropathy (CRION) is a recently described form of recurrent isolated subacute optic neuropathy, with accumulating evidence that it is a nosological distinct entity. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. Diagnosis and management of this condition is often challenging. This 33-year-old lady with family history of multiple sclerosis (MS), with uniocular visual loss of her right eye since 2 years old without apparent cause, presented with reduction of vision and loss of colour vision in the left eye, associated with painful eye movement. There was internuclear ophthalmoplegia but slit lamp examination were unremarkable. She had no other related sensory or motor symptoms. Magnetic resonance imaging (MRI) did not reveal any features of MS. Aquaporin-4 antibody, anti-MOG and gene testing for Leber’s hereditary optic neuropathy were all negative. Metabolic, infective, and other autoimmune causes were also excluded. Visual evoked potential studies of left eye showed a mild reduction in amplitude with no prolongation of latency. Her multiple optic neuritis recurrences were treated with intravenous steroids followed by tapering regime of oral prednisolone with good effect. Knowledge of this rare condition as part of the differential diagnoses of possible aetiologies of optic neuropathy is important among Ophthalmologists, as prompt diagnosis and steroid treatment helped reduce the associated risk of blindness. Multiple relapses after initial successful treatment of inflammatory optic neuropathy should raise the suspicion of CRION.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S19

Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report

BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder which often presents with neuropsychiatric symptoms. A large proportion of cases are associated with an identifiable tumor, most commonly ovarian teratoma. However, recent literature has also described an overlap of anti-NMDAR encephalitis and demyelinating syndromes. Cases have been reported of anti-NMDAR encephalitis in patients with ADEM, optic neuritis, myelitis and multiple sclerosis. This link is considered rare, however has important clinical implications as treatments and prognosis may differ.Case presentationA 33-year-old female with a history of multiple sclerosis presented with new-onset neuropsychiatric symptoms. After substance-induced psychosis was ruled out, she was admitted to the medical ward for work up of psychosis secondary to multiple sclerosis. However, the consultation-liaison psychiatry service noted atypical symptoms which were concerning for autoimmune encephalitis. Admission to a psychiatric inpatient ward was deferred. Anti-NMDAR encephalitis was diagnosed with CSF analysis demonstrating lymphocytic pleocytosis and anti-NMDAR antibodies. In addition to first-line treatment of encephalitis with steroids, second-line immunotherapies were also implemented given the patient’s underlining demyelinating syndrome. The patient’s neurologic and psychiatric symptoms began to improve.ConclusionsThere is literature to demonstrate a possible connection between anti-NMDAR encephalitis and demyelinating syndromes. As such, autoimmune encephalitis should be considered in patients with multiple sclerosis presenting with atypical symptoms. Determining the correct diagnosis is crucial to inform the appropriate treatment protocol, and to improve prognosis.

Comparison of the Structure and Function of the Retina and the Optic Nerve in Patients with a History of Multiple Sclerosis-Related Demyelinating Retrobulbar Optic Neuritis Treated and Not Treated with Systemic Steroid Therapy.

PurposeTo compare the structure and function of the retina and the optic nerve in patients with a history of multiple sclerosis (MS)-related demyelinating retrobulbar optic neuritis treated and not treated with systemic steroid therapy.Patients and MethodsThirty-two eyes of 32 MS patients with a past single episode of MS-related demyelinating retrobulbar ON were divided into 2 groups: S(+) consisting of 16 patients treated with intravenous methylprednisolone at a dose of 1g/day for 3 days during the acute stage of ON and S(-) consisting of 16 patients who did not receive any treatment. The following examinations were performed: distance best-corrected visual acuity (DBCVA) (Snellen), slit-lamp examination of the anterior and posterior segment of the eye (90D Volk lens), visual field analysis (Carl Zeiss Humphrey 750 Visual Field Analyzer, 24-2, W-W), macular thickness in the foveal (RT1) and parafoveal region (RT2), as well as peripapillary retinal nerve fiber layer thickness (RNFL) in the temporal, superior, nasal and inferior quadrants (Carl Zeiss Cirrus HD-OCT), assessment of the bioelectrical function of the visual pathway with an emphasis on the optic nerve – pattern visual evoked potentials (PVEP) and of macular ganglion cells and cone photoreceptors – pattern electroretinogram (PERG) (Roland Consult).ResultsNo statistically significant differences were observed between the investigated groups in terms of DBCVA, mean deviation of visual field macular (RT1, RT2) and RNFL thickness in the temporal, superior, nasal and inferior quadrants, as well as of the bioelectrical function (PVEP, PERG).ConclusionThe application of steroid therapy should be considered on an individual basis and not as a routine treatment for each patient.

MO323MEDICATION INDUCED RELAPSE OF FGSG

Abstract Background and Aims 31-year-old female with past medical history of Multiple Sclerosis diagnosed with Minimal Change Disease (MCD) in 2011. At diagnosis she had proteinuria that exceeded 7 g per day. She was treated with steroids and went into complete remission. In 2017 presented again with nephrotic syndrome and on repeat biopsy she was diagnosed with Focal Segmental Glomerulosclerosis (FSGS). She was restarted on steroids and had some improvement but despite 20 weeks of high dose steroids did not achieve remission. After every attempt of tapering, she would relapse. Method Other treatments tried without success were tacrolimus, cyclophosphamide and rituximab. Mild improvement with tacrolimus but stopped after a grand mal seizure. The lowest achievable steroid dose was 20mg daily. She was started on combination therapy tacrolimus and mycophenolate mofetil and was able to come off steroids and went into remission. Results After a few months of remission, she began to relapse. It was noted after extensive investigation that she had been placed on cabergolin for hyperprolactinemia by her endocrinologist at the time she began to relapse. Cabergolin was stopped and she went into remission again. We present the first case of FSGS relapse due to cabergolin. Conclusion Cabergoline is metabolized by hydrolysis and has limited cytochrome P450 (CYP) metabolism. Despite limited CYP metabolism, cabergoline does have an interaction with clarithromycin, a known inhibitor of CYP and p-glycoprotein. One rat study suggest that mycophenolate is a substrate for p-glycoprotein, so it is possible that there is some competitive inhibition. This would explain why the patient relapsed while on cabergoline and in remission after stopping it.

An Unusual Case of Bilateral Adrenal Hyperplasia

Background: Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of Castleman Disease, which is a rare lymphoproliferative disease that can be life threatening. Diagnosis is often delayed because of its nonspecific presentation. Bilateral adrenal hyperplasia has been a reported complication, however the majority of cases reported have been in Asian patients. Prior accounts of elevated ACTH in TAFRO have been in the context of adrenal insufficiency. Clinical Case: A 28-year-old Caucasian male with a history of multiple sclerosis was seen in the ED with abdominal pain. On presentation, he was afebrile and normotensive. Physical exam was notable for cervical lymphadenopathy and abdominal tenderness. There was no facial rounding/plethora, bruising, abnormal striae, or proximal muscle weakness. He had normal blood counts, serum chemistry and liver function. An abdominal CT scan showed marked bilateral adrenal hyperplasia with pre-aortic, peri-aortic and retroperitoneal lymphadenopathy. An 8AM serum cortisol was 14.1 mcg/dl (4.8–19.6 mcg/dl) and adrenocorticotrophic hormone (ACTH) was elevated at 152 pg/ml (7.2–63 pg/ml). A repeat serum 8AM cortisol following low dose dexamethasone suppression test (LDDST) was 14.7 mcg/dl, however at that point the patient had developed new fevers and thrombocytopenia. Blood pressure, blood glucose and potassium remained normal. An MRI of the brain showed a normal appearing pituitary gland. An extensive infectious and rheumatologic evaluation was negative, and he underwent an inguinal lymph node biopsy which showed nodal expansion with histiocytes, consistent with TAFRO. High dose methylprednisolone and Siltuximab (an IL-6 inhibitor) were started, and his fever and abdominal pain resolved. He was discharged home on oral prednisone. Conclusion: We describe a case of bilateral adrenal hyperplasia with elevated ACTH and non-suppressed cortisol on LDDST suggestive of ACTH-driven cortisol excess. However, interpretation of his LDDST is made difficult in the context of persistent fevers. Although we cannot definitively exclude pathologic hypercortisolism at this time, given his lack of suggestive features such as proximal muscle weakness, abnormal striae or hypokalemic alkalosis, his over-all presentation was more consistent with hyperplasia secondary to TAFRO rather than an underlying pathologic hypercortisolism. Adrenal hyperplasia has been noted in TAFRO, however its pathogenesis remains poorly understood. TAFRO should be added among the differentials for bilateral adrenal hyperplasia to facilitate early diagnosis and treatment.

A Case of Rare Autoimmune Pancytopenia Due to Graves’ Disease

Introduction: Graves’ disease has been associated with cytopenias, most commonly anemia. Pancytopenia is a rare complication and is not often encountered.Case Presentation: A 54-year-old woman with history of multiple sclerosis on alemtuzumab was referred for abnormal thyroid function tests. At the initial visit, the patient reported a 20-pound unintentional weight loss, tremors, sweating and heat intolerance. She was 3 years post-menopausal and had no history of recent viral illness, contrast exposure or family history of thyroid disease. Physical exam revealed an anxious appearing woman with fine tremors in both hands, hyperreflexia but no lid lag or exophthalmos. Labs included TSH <0.005 uIU/mL (0.400-4.2), free T4 2.89 ng/dL (0.80-1.50), TSH receptor binding antibody 8.24 IU/L (< 2.00), TSI 7.27 IU/L (<0.56), WBC 2900/uL (4500-11000), ANC 1746/uL (1900 - 8000), hemoglobin 11.4 g/dL (11.7-15.0) and platelet 207,000/uL (150,000-450,000). Thyroid ultrasound noted sub-centimeter hypoechoic/cystic nodules and 24-hour thyroid uptake showed 56.4% symmetric uptake (upper limit of normal 30%). Due to leukopenia, the patient was started on propranolol and underwent radioiodine ablation with 14.8 mCI. Two weeks later, she reported easily bruising and gum bleeding and her blood work was significant for pancytopenia. The patient was referred to hematology and two bone marrow samples were obtained. Though MDS/MPN was initially suspected based on atypia in both specimens, there were no immunophenotypic, cytogenetic or molecular abnormalities suggesting a neoplastic process. Instead the patient was thought to have autoimmune pancytopenia secondary to Graves’ and the atypia was believed to be secondary to peripheral consumption. She was started on prednisone 1 mg/kg/day with resolution of her cytopenias.Discussion: Graves’ disease has been associated with hematological abnormalities including isolated anemia (the most common), thrombocytopenia or leukopenia. Pancytopenia is an uncommon complication and is rarely described in the literature. The exact mechanism remains unclear, but may be related to either reduced production of hematopoietic cells from the bone marrow or increased destruction of mature hematopoietic cells due to autoantibodies. Since thyroid hormones are known to increase erythropoietin, this leads to an exaggerated consumption of iron, folic acid and vitamin B12 and can cause various forms of anemias. Leukopenia may be secondary to immunologic destruction whereas thrombocytopenia may be due to antiplatelet antibodies or increased splenic sequestration. Pancytopenia is rare. Our patient was treated with high dose prednisone with resolution of her pancytopenia, which suggests an autoimmune process as the mechanism. Our case showcases a rare complication of Graves’ disease and highlights that high dose steroid therapy may improve cytopenias associated with this condition.

Real-world Compliance With Percutaneous Tibial Nerve Stimulation Maintenance Therapy in an American Population

To evaluate percutaneous tibial nerve stimulation (PTNS) maintenance therapy dropout rates and identify factors associated with compliance in an American population. We retrospectively queried our PTNS database for patients from 2014-2019. Demographic, relevant clinical, and visit data were collected. Maintenance therapy was patient-driven and frequency of sessions was tapered based on symptomology. Upon completion of 12 initial sessions, we assessed dropout from maintenance at 3, 6, 9, and 12 months. Multiple variables were tested for correlation with dropout in patients continuing maintenance therapy for 1 year vs those who dropped out. One hundred and sixty-three PTNS patients were identified, of which 104 completed initial therapy and 81 proceeded with maintenance therapy. At 3, 6, 9, and 12 months, maintenance continuation rates were 77.8% (63/81), 58.0% (47/81), 45.6% (37/81), and 39.5% (32/41), respectively. Primary reasons for dropout were worsening of urinary symptoms/lack of efficacy (n=21), time commitment (n=9), loss of insurance (n=5), medical comorbidities (n=4), request for alternative OAB treatment (n=2), and unknown (n=8). On both univariate and multivariate analysis, perceived symptom improvement (P<.01; HR=0.02, P< .01) was associated with continuing maintenance therapy. On only univariate analysis, neurological history (P=.02) and multiple sclerosis history (0.02) were associated with continuing therapy. Only 39.5% of patients continue to undergo maintenance PTNS therapy after 1 year. Future studies are required to understand and ameliorate factors for low compliance in PTNS maintenance therapy.