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Understanding Types Of Nontuberculous Mycobacteria

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SOURCES:

CDC: "Healthcare-Associated Infections (HAIs) – Nontuberculous Mycobacteria (NTM)," "Healthcare-Associated Infections (HAIS) – Clinicians."

Clinics in Chest Medicine: "Nontuberculous Mycobacteria Infections in Immunosuppressed Hosts."

Annals of the American Thoracic Society: "Incidence and Prevalence of Nontuberculous Mycobacterial Lung Disease in a Large U.S. Managed Care Health Plan, 2088-2015."

Pathogens: "Non-Tuberculous Mycobacterial Diseases in Children."

UpToDate: "Overview of nontuberculous mycobacterial infections," "Treatment of lung infection with Mycobacterium kansasii and other less common nontuberculous mycobacteria in adults," "Buruli ulcer (mycobacterium ulcerans infection."

Merck Manual (Consumer Version): "Infections Caused by Bacteria Related to Tuberculosis (TB)."

Merck Manual (Professional Version): "Nontuberculous Mycobacterial Infections."

National Organization for Rare Disorders: "NIH Gard Information: Mycobacterium Avium Complex infections."

Journal of Pathogens: "General Overview on Nontuberculous Mycobacteria, Biofilms, and Human Infection."

Frontiers in Cellular and Infection Microbiology: "Mycobacterium abscessus complex: A Review of Recent Developments in an Emerging Pathogen."

Microbiology Spectrum: "Mycobacterium marinum."

Cleveland Clinic: "Nontuberculous Mycobacterial Infections."

American Lung Association: "Learn about NTM Lung Disease."

Tuberculosis & Respiratory Diseases: "Treatment of Mycobacterium avium Complex Pulmonary Disease."

Indian Journal of Medical Research: "Epidemiology, diagnosis & treatment of non-tuberculous mycobacterial diseases."

University of Notre Dame (College of Science): "Study sheds light on immune response in Mycobacterium avium Complex infection."

Legionnaires' Disease Following Lake Swimming In Iowa

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Atypical Parkinsonism

Parkinsonism refers to a set of symptoms typically seen in Parkinson's disease but caused by other disorders. Atypical parkinsonism includes a variety of neurological disorders in which patients have some clinical features of PD, but the symptoms are caused not only by cell loss in the substantia nigra (the brain area most affected in classic PD), but also by added degeneration of cells in the parts of the nervous system that normally contain dopamine receptors (striatum). In other words, the patients look like they have PD, but the cause of their symptoms is different from that of "classic" PD.

Symptoms and Types of Atypical Parkinsonism

Patients with atypical parkinsonism have symptoms like PD, including resting tremors, slowed movement, stiffness, gait difficulty and postural instability, but have additional symptoms and signs that are not typically present in PD. This has led to the commonly used term "parkinsonism plus syndrome." A few such syndromes that are well described and, like PD, are thought to be related to the abnormal accumulation of proteins such as alpha-synuclein ("synucleinopathy") or tau ("tauopathy").

The additional symptoms and signs may include inability to look up and down (vertical gaze palsy) and early postural instability leading to frequent backward falls, such as seen in progressive supranuclear palsy (PSP – a tauopathy), the most common form of atypical parkinsonism. Patients with PSP often have the "procerus sign" which is a particularly "worried" facial expression.

The second most common form of atypical parkinsonism is multiple system atrophy (MSA – a synucleinopathy). Patients with MSA are typically distinguished from those with PD by the presence of autonomic features such as unstable blood pressure (particularly orthostatic hypotension, which refers to drops in blood pressure when standing), early disturbance of sexual, bladder and bowel dysfunction, reddish-blue discoloration of skin (the "cold hand" sign), and marked sleep disturbance (e.G. Acting out dreams and sleep apnea). Other typical features of MSA include forward head tilt (anterocollis) or a body tilt when sitting (Pisa sign), loss of coordination, and a rapidly progressive course with inability to ambulate usually within the first three to five years of onset. MSA is divided into MSA-C (cerebellar type) which has more symptoms of ataxia (incoordination) and MSA-P (parkinsonian type) which has more parkinsonian symptoms but is relatively unresponsive to the usual therapy for Parkinson's disease (i.E., levodopa). 

Some of the atypical parkinsonian disorders, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), vascular parkinsonism (VP) are discussed in separate articles on the website (www.Jankovic.Org).

Dementia with Lewy Bodies (DLB) - DLB patients, in addition to the parkinsonian features, early dementia (usually preceding or co-occurring with the parkinsonian symptoms) and visual hallucinations (seeing people, small animals or objects that are not real) with their symptoms typically fluctuating leading to "good days" and "bad days." DLB is a synucleinopathy.

Corticobasal Syndrome (CBS) - CBS patients usually present with asymmetric stiffness, apraxia (inability to carry out learned purposeful movements), alien limb (the hand or the leg seem to have "a mind of their own"), and limb dystonia (abnormal sustained muscle contractions causing abnormal postures and twisting) or myoclonus (sudden jerking). CBS is a tauopathy.

Another common cause of atypical parkinsonism is "vascular parkinsonism" caused by multiple and usually very small strokes. These patients tend to have more symptoms in the lower extremities (lower body parkinsonism) with walking difficulties, balance problems and falls.

The various atypical parkinsonian syndromes are classified according to the patterns of damage they produce in the nervous system, the constellation of clinical symptoms they cause, and their natural course.

Cause, Diagnosis and Treatment

Poor or no response to levodopa is a common feature to all forms of atypical parkinsonism. In contrast to typical PD, in which dopamine receptors are spared, patients with atypical parkinsonian disorders have lost their dopamine receptors and therefore they do not respond to levodopa as well as those with typical PD. This can be demonstrated by special imaging such as positron emission tomography (PET) and dopamine transporter imaging (DAT-SPECT). MRI may be also helpful in differentiating PD from atypical parkinsonism.

There are probably many causes of atypical parkinsonism, but no one specific cause has been identified. Usually only one member of a family is affected and, therefore, these disorders are thought to be sporadic and not inherited. There is much active research into the causes of these disorders.

Since 2023, Baylor Parkinson's Disease and Movement Disorders Center (PDCMDC) has started to use a cutting-edged diagnostic tool, named SynOne skin biopsy test to help differentiate Parkinson's disease from atypical parkinsonism. You may discuss with your movement disorders neurologist at PDCMDC to see if this would be the test necessary for you. 

Also since 2023, Baylor PDCMDC has been designated by the CurePSP Foundation as the Center of Care for PSP, CBD, and MSA based on our commitment and excellence to take care of and expand resources for people with atypical parkinsonism. One of our missions is to expand the research on atypical parkinsonism. Because the various atypical parkinsonism diseases are relatively uncommon, it is difficult to obtain public funding for research. Therefore, research into these disorders largely depends upon private contributions, particularly from patients and families affected with the diseases. Besides financial support and willingness to participate in clinical research projects, scientists are interested in examining postmortem brains of patients who were afflicted with these disorders. 

Table 1. Parkinsonism Plus Syndromes: Differential Diagnosis   PD PSP MSA-P MSA-C CBD DLB PDACG Bradykinesia + + + ± + ± + Rigidity + + + + + ± + Gait Disturbance + + + + + ± + Tremor + - - ± ± - + Ataxia - - - + - - ± Dysautonomia ± ± ± ± - ± ± Dementia ± + - - ± + + Dysarthria/Dysphagia ± + + + + ± + Dystonia ± ± ± - + - - Eyelid Apraxia - + ± - ± - ± Limb Apraxia - - - - + ± - Motor Neuron Disease - - ± - - - + Myoclonus ± - ± ± + ± - Neuropathy - - - ± - - - Oculomotor Deficit - + - + + ± ± Sleep Impairment ± ± ± ± - ± - AsymmetricFindings + - ± - + - - LevodopaResponse + ± ± ± - - - LevodopaDyskinesia + - ± - - - - Family History ± - - - - - - Putaminal T-2 Hypo-Intensity - ± + + - - - Lewy Bodies + - ± ± ± + - Abbreviations

CBD = cortical-basal ganglionic degeneration

DLB = dementia with Lewy bodies

MSA-C = multiple system atrophy, predominantly cerebellar

MSA-P = multiple system atrophy, predominantly cerebellar

PD = Parkinson's disease

PDACG = parkinsonism-dementia-amyotrophic lateral sclerosis complex of Guam

PSP = progressive supranuclear palsy

Selected References

Deutschländer AB, Ross OA, Dickson DW, Wszolek ZK. Atypical parkinsonian syndromes: a general neurologist's perspective. Eur J Neurol. 2018;25(1):41-58. 

Jankovic J, Tan EK. Parkinson's disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 2020;91(8):795-808.

Jankovic J, Hallett M, Okun M, Comella C, Fahn S. Principles and Practice of Movement Disorders, Elsevier, Philadelphia, PA, 2022.

Jankovic J. Parkinson's Disease and Other Movement disorders. Chapter 96; In: Jankovic J, Maziotta J, Newman N, Pomeroy S, eds. Bradley and Daroff''s Neurology in Clinical Practice, 8th Edition, Elsevier, Philadelphia, PA, 2022.

Jecmenica Lukic M, Kurz C, Respondek G, et al. Copathology in Progressive supranuclear palsy: Does it matter?. Mov Disord. 2020;35(6):984-993.

Kovacs GG, Lukic MJ, Irwin DJ, et al. Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol. 2020;140(2):99-119.

Marques TM, van Rumund A, Oeckl P, et al. Serum NFL discriminates Parkinson disease from atypical parkinsonisms. Neurology. 2019;92(13):e1479-e1486.

Mehanna R, Jankovic J. Young-onset Parkinson's disease: Its unique features and their impact on quality of life. Parkinsonism Relat Disord. 2019;65:39-48. Miki Y, Foti SC,

Asi YT, Tsushima E, Quinn N, Ling H, Holton JL. Improving diagnostic accuracy of multiple system atrophy: a clinicopathological study. Brain. 2019;142(9):2813-2827.

Niemann N, Jankovic J. Juvenile parkinsonism: Differential diagnosis, genetics, and treatment. Parkinsonism Relat Disord. 2019;67:74-89.

Picillo M, Tepedino MF, Abate F, et al. Midbrain MRI assessments in progressive supranuclear palsy subtypes. J Neurol Neurosurg Psychiatry. 2020;91(1):98-103.

Rizzo G, Arcuti S, Copetti M, et al. Accuracy of clinical diagnosis of dementia with Lewy bodies: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2018;89(4):358-366.

Savica R, Boeve BF, Mielke MM. When do α-synucleinopathies start? An Epidemiological Timeline: A Review. JAMA Neurol. 2018;75(4):503-509.

Stamelou M, Giagkou N, Höglinger GU. One decade ago, one decade ahead in progressive supranuclear palsy. Mov Disord. 2019;34(9):1284-1293.

Waln O, Jankovic J. Neuro-ophthalmology of movement disorders. Expert Review of Ophthalmology 2018;13(5):283–292.

Yamasaki TR, Holmes BB, Furman JL, et al. Parkinson's disease and multiple system atrophy have distinct α-synuclein seed characteristics. J Biol Chem. 2019;294(3):1045-1058.

Resources

CurePSP Hope Line 800-457-4777Direct 919-525-8355https://www.Psp.Org/www.MultipleSystemAtrophy.Org

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