Primary progressive multiple sclerosis is a well-recognized form of multiple sclerosis that is characterized by progressive damage to the central nervous system (CNS) and subsequent decline in overall functioning and quality of life [1] [2] [3] [4]. The exact pathogenic mechanism by which neuronal degeneration occurs, however, remains unclear [1] [4]. It is recognized in about 10-15% of all cases suffering from MS and is one of the rare entity that equally affects both genders [1] [5] [4] [6] [7]. In fact, some studies propose that males are more frequently affected than females and that MS patients are more likely to develop PPMS at an older age [1] [2] [7]. Compared to relapsing-remitting multiple sclerosis (RRMS), which encompasses the vast majority of MS patients and presents with optic neuritis and other isolated spinal cord/brainstem abnormalities [2], the clinical presentation of PPMS is comprised of two main symptoms - spastic paraplegia (often described with an unclear sensory level) and ataxia [2] [5]. These signs appear due to progressive atrophy of the spinal cord and the cerebellum, whereas the appearance of brainstem abnormalities, visual deficits, sexual dysfunction, cognitive decline, and inability to maintain sphincter control, are less commonly reported in PPMS [1] [2] [7]. Primary progressive multiple sclerosis has a poor prognosis than other types of MS, mainly because of a delayed diagnosis and an aggressive neurological deterioration [5] [7].

• Weakness

  Facial numbness and weakness are also common. [medical-dictionary.thefreedictionary.com]

  A: PPMS frequently is associated with weakness in the legs and difficulty walking. In one study, over 90% of patients with PPMS had weakness in the legs. Seunggu Han, MD Answers represent the opinions of our medical experts. [medicalnewstoday.com]

  For the PPMS cohort, a syndrome consistent with isolated myelopathy was found in 36% of patients (n=30) and arm weakness without leg weakness did not occur. [jamanetwork.com]

  Common early symptoms of PPMS include weakness in the legs and problems with walking. These symptoms typically get worse over a period of two years. [healthline.com]

• Fatigue

  Fatigue Fatigue is one of the most common symptoms in MS reported by up to 95% of pwMS. [hindawi.com]

  “We also have additional data that shows we have an effect on fatigue (a very important aspect of MS, 75% of patients have fatigue). [mdmag.com]

  Fatigue is also common with this and all other forms of multiple sclerosis. [verywell.com]

  It means those with the primary progressive form of the disease can now begin receiving twice-yearly infusions of ocrelizumab, which delays the symptoms of multiple sclerosis, such as difficulty walking, fatigue and blurred vision, for as long as possible [almondcare.co.uk]

  Fatigue is very common. This is not normal tiredness but an exhaustion which is out of all proportion to the task that has been undertaken. Fatigue can be mental or physical tiredness. Not all symptoms are obvious to other people. [mstrust.org.uk]

• Difficulty Walking

  It means those with the primary progressive form of the disease can now begin receiving twice-yearly infusions of ocrelizumab, which delays the symptoms of multiple sclerosis, such as difficulty walking, fatigue and blurred vision, for as long as possible [almondcare.co.uk]

  Progression can be severe, and some people with PPMS may experience difficulty walking, mood changes, balance problems, visual disturbances, bladder and bowel difficulties, and fatigue. [medicalnewstoday.com]

  Classic symptoms of PPMS, according to Coyle, include difficulty walking, leg weakness, and muscle spasticity. [everydayhealth.com]

  Other chronic symptoms that patients with MS experience can include fatigue, difficulty controlling bladder function, trouble with walking, and/or changes in sleep patterns and mood. [medicalxpress.com]

• Falling

  Somewhere between 2 percent to 5 percent of all MS cases fall into the pediatric category, affecting anywhere from 8,000 to 20,000 children. Several thousand more children and teens may have symptoms of MS, but no firm diagnosis. [sharecare.com]

  If this happens I informed this patient he may fall outside of the licensed indication, for example his PPMS may not be active enough. In addition, if and when the EMA licenses ocrelizumab for PPMS then NICE has to green-light it for use in the NHS. [multiple-sclerosis-research.blogspot.com]

  First, 85 percent of individuals diagnosed with MS begin with the RRMS form, and after many years, RRMS usually advances to SPMS – so clearly the vast majority of patients fall under these categories. [mymsaa.org]

  In the clinical trial data released last fall, which covered 732 people with primary progressive MS, people who took the drug had a 24 percent reduction in the progression of disability after 12 weeks compared to those who received a placebo. [statnews.com]

  Psoriaze uz galvas neka izraisita Falls -- especially those to the side -- are. [itdiabi.duckdns.org]

• Dysphagia

  MS can cause a variety of symptoms, including changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia [disabled-world.com]

  Dysphagia occurs in about 34%–43% of pwMS [98, 99]. Fatigue, tremors, weakness, and incoordination exacerbate dysphagia and dysarthria. Spasticity is worsened by malnutrition. [hindawi.com]

• Muscular Atrophy

  In late-stage Roche, they have treatments that are being tested for Alzheimer’s disease, Autism, and for Spinal Muscular Atrophy. [mdmag.com]

  atrophy type 1） 二型X染色体相关的脊髓性肌肉萎缩症（英语：X-linked spinal muscular atrophy type 2） 一型家族远端型脊肌萎缩症（英语：Distal spinal muscular atrophy type 1） 先天性远端型脊肌萎缩症（英语：Congenital distal spinal muscular atrophy） 脊肌萎缩症伴有小脑发育不全（英语：Spinal muscular atrophy with pontocerebellar [beichengjiu.com]

  脊髄性筋萎縮症 Spinal muscular atrophy, SMA Type I 脊髄性筋萎縮症（SMA Type I） 1 HPS0158 HPS0159 Spinal muscular atrophy, SMA Type II 脊髄性筋萎縮症（SMA Type II） 1 不要 有 HPS1391 HPS1392 HPS1393 HPS1394 HPS1395 HPS1396 Spinal muscular atrophy 脊髄性筋萎縮症 1 不要 HPS0932 HPS0933 HPS0934 [cell.brc.riken.jp]

  Roche has more than a dozen investigational medicines in clinical development for diseases that include multiple sclerosis, Alzheimer’s disease, spinal muscular atrophy, Parkinson’s disease and autism. [mynewsdesk.com]

• Blurred Vision

  It means those with the primary progressive form of the disease can now begin receiving twice-yearly infusions of ocrelizumab, which delays the symptoms of multiple sclerosis, such as difficulty walking, fatigue and blurred vision, for as long as possible [almondcare.co.uk]

  The damage stops messages from being passed along the nerves, leading to symptoms including tiredness and blurred vision. Ocrelizumab works by killing the cell which attacks the myelin sheath. [telegraph.co.uk]

  Problems with vision This can include double vision, blurred vision, inability to identify colors and contrasts, and pain when moving your eyes. [healthline.com]

  The main symptoms include: fatigue difficulty walking vision problems, such as blurred vision problems controlling the bladder numbness or tingling in different parts of the body muscle stiffness and spasms problems with balance and co-ordination problems [nhs.uk]

  Other initial symptoms were disturbances of sensation (paresthesias, numbness, or Lhermitte sign) (18% [n=15]), blurred vision (7% [n=6]), and urinary dysfunction (4% [n=3]). [jamanetwork.com]

• Visual Impairment

  This proportion would have risen to 54% if uncorrectable mild visual impairment or the presence of optic disc pallor had been ignored. [jamanetwork.com]

  Gait is impaired by weakness, spasticity, incoordination, balance, fatigue, and visual disturbances. [hindawi.com]

• Facial Numbness

  Facial numbness and weakness are also common. [medical-dictionary.thefreedictionary.com]

• Euphoria

  Side effects have included weakness, dizziness, relaxation, and incoordination, as well as euphoria. As a result, marijuana is not recommended as an alternative treatment. [medical-dictionary.thefreedictionary.com]

• Mood Swings

  Patient discussion about multiple sclerosis Q. does multiple sclerosis cause mood swings seem like i have changed. I 've become very irritable towards my family. Seems like I've become a mean person, and that has not my charactor. A. [medical-dictionary.thefreedictionary.com]

• Cognitive Impairment

  cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. [ncbi.nlm.nih.gov]

• Ataxia

  Spastic paraparesis and progressive ataxia are principal symptoms in this subset of patients. [symptoma.com]

  Abstract HDLS (Hereditary Diffuse Leukodystrophy with Spheroids) is a hereditary leukodystrophy whose main clinical manifestations include parkinsonism, spasticity, and ataxia. [ncbi.nlm.nih.gov]

  ICD-10-CM G35 is grouped within Diagnostic Related Group(s) (MS-DRG v 36.0): 058 Multiple sclerosis and cerebellar ataxia with mcc 059 Multiple sclerosis and cerebellar ataxia with cc 060 Multiple sclerosis and cerebellar ataxia without cc/mcc Convert [icd10data.com]

  This condition, known as progressive cerebellar syndrome (PCS), is seen less often than progressive myelopathy but can manifest with: Tremor: Impairment of fine hand movement due to severe intention tremor Hypotonia: Loss of muscle tone Gait ataxia: Loss [verywell.com]

  However, other people have what is called “cerebellar syndrome,” which is characterized by severe ataxia and problems with balance. [verywellhealth.com]

• Dizziness

  Symptoms of the latter may include itchy skin, rash, hives, skin redness, flushing, low blood pressure, fever, fatigue, dizziness, headache, throat irritation, and shortness of breath. [clinicaladvisor.com]

  Symptoms These are symptoms of MS: Trouble walking Vision problems Muscle weakness Difficulty staying balanced Paralysis Numbness Prickling sensations Dizziness Shakiness Difficulty thinking clearly Mood changes Depression Sexual dysfunction Trouble with [columbianeurology.org]

  Dizziness Those with PPMS may have episodes of dizziness and lightheadedness. Others may experience vertigo, a sensation that they’re spinning and losing their balance. [healthline.com]

  […] vision Spasticity or stiffness of the muscles Difficulty controlling the bladder or bowels Problems with cognition, such as learning and memory or information processing Difficulty with walking and coordination Trouble walking Muscle weakness Paralysis Dizziness [cedars-sinai.edu]

  […] and feet, back pain, and muscle spasms) Electric-shock sensations that run down the back and limbs when the neck is bent (Lhermitte sign) Trouble walking Vision problems Muscle weakness Trouble staying balanced Paralysis Numbness Prickling feelings Dizziness [hopkinsmedicine.org]

• Tremor

  This worsening usually affected the ability to walk and was less likely to cause visual symptoms or tremor. Generally, thinking, memory, and intellect are relatively spared with PPMS. [my.clevelandclinic.org]

  Symptoms in-clude pain, weakness, numbness, tingling, paralysis, tremors, and muscle dysfunction. [medical-dictionary.thefreedictionary.com]

  This condition, known as progressive cerebellar syndrome (PCS), is seen less often than progressive myelopathy but can manifest with: Tremor: Impairment of fine hand movement due to severe intention tremor Hypotonia: Loss of muscle tone Gait ataxia: Loss [verywell.com]

  Symptomatic treatment for tremor includes identification of type of tremor, trigger factors and part of body involved. Use of assistive devices (braces and support) and evaluation for therapy may be helpful. [hindawi.com]

• Lhermitte Sign

  Symptoms can include: Pain (for example, headaches, pain in the legs and feet, back pain, and muscle spasms) Electric-shock sensations that run down the back and limbs when the neck is bent (Lhermitte sign) Trouble walking Vision problems Muscle weakness [hopkinsmedicine.org]

  Some people experience Lhermitte sign, which is an electrical shock-like sensation that runs down the back and into the limbs. This sensation usually occurs when the head is bent forward. [icdlist.com]

  Lhermitte sign urinary incontinence others: fatigue depression Uhthoff phenomenon: heat and exercise worsen symptoms cognitive decline Classification A number of patterns of longitudinal disease have been described 11,12 : relapsing-remitting most common [radiopaedia.org]

• Sexual Dysfunction

  These may address problems like depression, sexual dysfunction, and fatigue. Prevention Experts don't know of a way to prevent MS. But if your body temperature goes up, it may make your symptoms worse for a short time. [columbianeurology.org]

  These signs appear due to progressive atrophy of the spinal cord and the cerebellum, whereas the appearance of brainstem abnormalities, visual deficits, sexual dysfunction, cognitive decline, and inability to maintain sphincter control, are less commonly [symptoma.com]

  dysfunction Causes and Risk Factors Ten percent of all multiple sclerosis patients are diagnosed with PPMS. [cedars-sinai.edu]

  A person with PPMS may also experience the following symptoms: changes in mood muscle weakness numbness a tingling sensation unclear or muddled thought fatigue balance problems vision problems problems with bowel and bladder control sexual dysfunction [medicalnewstoday.com]

• Urinary Incontinence

  incontinence others: fatigue depression Uhthoff phenomenon: heat and exercise worsen symptoms cognitive decline Classification A number of patterns of longitudinal disease have been described 11,12 : relapsing-remitting most common (70% of cases) patients [radiopaedia.org]

  Training in bowel and bladder care may be needed to prevent or compensate for incontinence. [medical-dictionary.thefreedictionary.com]

  Figure 4 provides a flow chart for managing urinary incontinence in patients with long-term neurological conditions including PPMS [39]. Symptomatic lower urinary tract infections should be treated on the basis of a positive urine culture. [hindawi.com]

• Urinary Retention

  Therapeutic measures include medications to diminish muscle spasticity; measures to overcome urinary retention (such as credé's method or intermittent catheterization ); speech therapy; and physical therapy to maintain muscle tone and avoid orthopedic [medical-dictionary.thefreedictionary.com]

Because the various clinical forms of MS might be indistinguishable in their initial stages [2], particularly the different types of progressive MS, the physician, with his/her ability to obtain a detailed patient history and conduct a thorough physical examination, plays a crucial role in recognizing MS early on. Firstly, key information regarding the presence of symptoms, their duration, as well as progression, should be obtained, followed by a meticulous neurological evaluation. In recent years, diagnostic criteria for identifying PPMS have been designed and consist of the following [2] [4] [5] [7]:

• Progression of the disease for at least a period of 1 year.
• MRI findings - Either 9 lesions on T2-weighted studies or ≥ 4 lesions on T1-weighted studies in the brain, each exhibiting positive visual evoked potentials (VEP), or at least 2 focal spinal cord lesions seen on T2-weighted studies. Two out of three of the mentioned findings are required for the diagnosis of PPMS [3].
• The presence of oligoclonal bands or abnormally high levels of immunoglobulin (Ig) G antibodies in the CSF.

• Abnormal Visual Evoked Potentials

  visual evoked potential MR imaging lack of viable alternative diagnosis The exact etiology is poorly known although it is believed to have both genetic and acquired contributory components. [radiopaedia.org]

OBJECTIVES: To investigate, during the 5-year period without treatment after termination of a 2-year clinical trial of interferon beta-1b for the treatment of primary progressive multiple sclerosis, differences in the evolution of clinical variables and [ncbi.nlm.nih.gov]

Primary Progressive Multiple Sclerosis (PPMS) Menu What is the prognosis for primary progressive multiple sclerosis? As with multiple sclerosis in general, the prognosis varies in PPMS. [my.clevelandclinic.org]

BACKGROUND: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. [ncbi.nlm.nih.gov]

Primary progressive multiple sclerosis has a poor prognosis than other types of MS, mainly because of a delayed diagnosis and an aggressive neurological deterioration. [symptoma.com]

But it is a prognosis snapshot for today, based on clinical signs and tests results that might aid a longer term estimate of progression. [multiplesclerosisnewstoday.com]

This progressive etiology would provide valuable insight into PPMS development and may also shed light on SPMS progression. [clinicaltrials.gov]

Abstract Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. [ncbi.nlm.nih.gov]

結節性硬化症 Tuberous sclerosis complex （TSC), unknown genetic etiology 結節性硬化症、遺伝子型不明 1 不要 有 HPS2395 HPS2396 HPS2397 HPS2398 HPS2399 HPS2400 159. [cell.brc.riken.jp]

[…] various investigations (see McDonald diagnostic criteria for multiple sclerosis ), including 19 : typical history oligoclonal bands in CSF immunoglobulin G in serum abnormal visual evoked potential MR imaging lack of viable alternative diagnosis The exact etiology [radiopaedia.org]

Adams et al., Principles of Neurology, 6th ed, p903) Chronic disease characterized by presence of numerous areas of demyelination in the central nervous system with symptoms such as weakness, incoordination, paresthesis, and speech disturbances; the etiology [icd10data.com]

The objective of this study was to perform an updated systematic review of the epidemiology of PPMS in LATAM. METHODS: We conducted a systematic review of published epidemiological articles of PPMS from January 1997 to June 2017. [ncbi.nlm.nih.gov]

A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models. Health Technol Assess2002; 6: 1-73. [journals.sagepub.com]

METHODS Diagnosis and categorisation were performed by two neurologists, potential cases being identified from the following sources: neurology outpatient clinics; neurology inpatients; a review of hospital discharges; and an ongoing epidemiological study [jnnp.bmj.com]

[…] thalamus and visual cortex volume (respectively, p = 0.01 and p CONCLUSION: Our results suggest that RNFL thinning and GCIPL thinning/MV decrease may be explained by alternative mechanisms including retrograde trans-synaptic degeneration and/or a common pathophysiologic [ncbi.nlm.nih.gov]

It is generally now accepted that so-called ‘normal-appearing’ tissue in the MS brain and spinal cord is not normal, and that diffuse tissue damage particularly affecting neurons and axons plays the major pathophysiological role in progression—so that [jnnp.bmj.com]

Unfortunately, the lack of any warning symptoms hampers any future prevention trial in this population. [mayoclinic.pure.elsevier.com]

Prevention Experts don't know of a way to prevent MS. But if your body temperature goes up, it may make your symptoms worse for a short time. As a result, you may want to avoid overheating. [columbianeurology.org]

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