Mixed Dysarthrias

Mixed Dysarthrias

Definition

• Mixed dysarthrias involve neuro deficits distributed across two or more divisions of the nervous system.
• Damage causing dysarthria often occurs in multiple systems, unlike isolated neurological insults.
• Mixed dysarthrias are common.

Incidence

• Mayo Clinic data:
  • Mixed dysarthrias account for $26.4\%$ of all dysarthrias and $24.8\%$ of all MSDs.
  • Degenerative diseases cause $78\%$.
  • A combination of degenerative and vascular diseases causes $84\%$.

Etiologies

• Mixed dysarthrias often result from combined neurologic events or degenerative diseases.
• Degenerative diseases:
  • ALS (Amyotrophic Lateral Sclerosis)
  • Progressive Supranuclear Palsy
  • Corticobasal Degeneration
  • Multiple System Atrophy
  • Friedreich's Ataxia
  • Spinocerebellar Ataxias
  • Chronic Traumatic Encephalopathy
• Vascular disorders:
  • Multiple strokes
• Other causes:
  • Demyelinating disease (Multiple Sclerosis)
  • Toxic-metabolic conditions (Wilson's disease, manganese toxicity, hypoxic encephalopathy, osmotic Demyelination Syndrome - Central Pontine and Extrapontine Myelinolysis, Hepatocerebral Degeneration)
  • Trauma, head injuries
  • Neoplasm
  • Infectious and Autoimmune diseases

Neuro Basis

• Neurological damage crosses anatomical boundaries, affecting various motor system components simultaneously.
  • Example: A brainstem stroke can affect both UMN and LMN as both are located in the brainstem.
• UMN course down to the brainstem to synapse with LMN in cranial and spinal nerves; LMN cell bodies are in the brainstem. A single insult can damage both UMN and LMN.
• Nearly any combination of pure dysarthrias can occur, depending on the severity of neurological damage.
• Relative prominence of each type varies with the location and extent of neurological damage, resulting in variability.
• One component may be more prominent than others, they may be similar in severity, or they can change over time due to progressive disease processes.

Common Mixed Dysarthria Types and Associated Disorders

• Spastic-flaccid: Amyotrophic Lateral Sclerosis (ALS)
• Hypokinetic-spastic-ataxic: Multiple System Atrophy (MSA) (particularly with stridor)
• Hypokinetic-spastic: Progressive Supranuclear Palsy (PSP)
• Spastic-ataxic: Corticobasal Degeneration (CBD) (may also demonstrate apraxia of speech), Multiple Sclerosis
• Any combination of dysarthrias is possible.

Clinical Presentations

• Motor neuron disease: Progressive loss of UMNs or LMNs, or both.
• Progressive muscular atrophy (spinal muscle atrophy):
  • Affects LMNs only.
  • Characterized by progressive limb wasting/weakness, with or without cranial nerve weakness.
  • Can be congenital or emerge in childhood or adulthood.
  • If dysarthria is present, it is flaccid.
• Progressive bulbar palsy (PBP):
  • Mainly LMN weakness of cranial nerve muscles.
  • Dysphagia and dysarthria are predominant signs.
  • UMN signs in bulbar muscles may or may not be present.
  • When confined to LMN, dysarthria is flaccid.
  • Can be thought of as ALS without limb involvement.
• Primary Lateral Sclerosis (PLS) or Progressive Pseudobulbar Palsy:
  • Primarily affects bulbar muscles, affecting UMNs only.
  • Characterized by corticospinal or cortico-bulbar tract signs, or both, but without LMN involvement.
  • Can be difficult to distinguish from ALS.
  • $75\%$ of patients with PLS meet criteria for ALS within 4 years.
  • Associated with spastic dysarthria.
• Amyotrophic Lateral Sclerosis (ALS):
  • Most common motor neuron disease.
  • Characterized by UMN and LMN signs in the limbs (spinal nerves) or bulbar muscles, or both.
  • Associated with mixed spastic-flaccid dysarthria.
  • Affects men more than women.
  • Occurs sporadically, but $10\%$ of cases are familial.
  • Course is 2-5 years but may extend to 12.
  • Death is usually related to respiratory failure.
  • First signs are usually in the limbs, but $25\%$ may have first signs in bulbar muscles.
  • Dysarthria, dysphagia, and respiratory problems are initial symptoms.
  • If present with bulbar symptoms initially, tend to more rapid decline due to dysarthria and dysphagia.
  • Eye movements and autonomic and cognitive functions are usually spared, but may also see dementia or signs of parkinsonism; cognitive deficits more in those presenting with bulbar onset of symptoms.
• Progressive Supranuclear Palsy (PSP):
  • Multisystem neurodegenerative disease of unknown etiology, often mistaken for PD.
  • Considered a tauopathy (abnormal aggregation in the brain of tau protein).
  • Affects basal ganglia, midbrain, and brainstem.
  • Characterized by supranuclear ophthalmoparesis (paralysis of vertical gaze, especially downward gaze), postural instability with early falls, and signs of parkinsonism (tremor not prominent).
  • Doesn’t respond to Parkinson drugs.
  • Dysarthria and dysphagia (pseudobulbar palsy) are often early and prominent signs.
  • Spastic and hypokinetic dysarthria are supportive diagnostic features.
  • Behavioral and cognitive changes associate with frontal lobe dysfunction (apathy, irritability, difficulty in planning and sequencing, apraxia of speech) can be present. Occasionally are dominant.
  • Several dysarthria types are possible due to multisystem degeneration: mixed with various combinations of hypokinetic, spastic, and ataxic. Apraxia of speech is uncommon, but it can be the initial symptom.
• Corticobasal Degeneration or Corticobasal Syndrome (CBS):
  • Uncommon neurodegenerative disease.
  • Characterized by cortical and extrapyramidal signs.
  • Striking feature: asymmetry of initial signs and symptoms, even though disease eventually involves the cortex and basal ganglia bilaterally.
  • Asymmetric limb rigidity and apraxia. Myoclonus, tremor, and cortical sensory loss less common.
  • Alien limb phenomena (involuntary extremity movements) and mirror movements (involuntary movements that mirror those of the contralateral limb) are associated with parietal lobe damage.
  • Dysarthria is often mixed: Spastic and hypokinetic types most common, but can see hyperkinetic and ataxic components, too.
• Friedreich's Ataxia:
  • Inherited, autosomal recessive degenerative disease.
  • Predominantly spinocerebellar, but can be associated with spasticity, weakness, and extrapyramidal movement disorders.
  • Associated with ataxic and spastic dysarthria.
• Multiple System Atrophy:
  • Not a single disorder but a group of degenerative disorders.
  • Sporadic neurodegenerative condition: synucleinopathy (abnormal aggregation of protein ( alpha-synuclein, in the cytoplasm of neurons and glia)-MSA, PD, and dementia with Lewy bodys are synucleopathies.
  • Characterized by various combos of parkinsonism, ataxia, spasticity, and autonomic dysfunction (orthostatic hypotension) and cognitive impairment (frequently)
  • Like PSP, often mistaken for PD.
  • Label of MSA now used for other conditions: striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome.
  • $2$ subtypes: MSA-P (parkinsonism features predominating) and MSA-C (cerebellar features predominating).
  • MSA-P: dysarthria is hypokinetic or in combo with spastic and/or ataxic
  • MSA-C: dysarthria predominantly ataxic or incombo with spastic and/or hypokinetic
  • Shy-Drager also with autonomic deficits as well as spastic/ataxic/hypokinetic dysarthria
  • Thus basal ganglia and cerebellar control circuits as well as UMN pathways to have all $4$ types of dysarthrias: spastic, ataxic, hypokinetic and hyperkinetic
• Spinocerebellar Ataxias:
  • Associated with more than cerebellar involvement.
  • Can have brain stem, basal ganglia, cortex, spinal cord, and peripheral nerves.
  • Associated with combos of ataxic, spastic, hypokinetic, hyperkinetic, and flaccid dysarthria.
  • Mixed dysarthria is possible in any of the SCA subtypes that have more than one component of the motor system affected.
• Chronic Traumatic Encephalopathy:
  • Pathology is often associated with a history of repetitive brain trauma.
  • Associated with contact sports but can occur in anyone with repetitive concussions and subconcussive physical trauma (combat soldiers, physical abuse victims).
  • When progressive, it's considered neurodegenerative.
  • Form of tauopathy
  • Characterized by abnormalities in cognition, behavior, and mood.
  • Motor signs are not uncommon.
  • Dysarthria usually is mixed: hypokinetic or ataxic.

Vascular Causes

• Multiple strokes: can have any combo of dysarthrias. Spastic-ataxic is most common.
• Single brainstem strokes can have mixed dysarthria due to close proximity of extrapyramidal and pyramidal fibers, the cerebellar control circuit, and cranial nerve nuclei.
• Brainstem strokes tend to produce combos of spastic, ataxic, and flaccid dysarthria. Hyperkinetic dysarthria due to palatal-laryngeal tremor may co-occur.

Demyelinating Disease: Multiple Sclerosis

• Most common acquired demyelinating CNS disease. May be autoimmune disease.
• Affects women more than men; occurs between $20-40$ years of age, $100$ in $100,000$.
• Scattered and diverse areas of CNS affected, primarily white matter and periventricular areas, the brainstem, spinal cord, and optic nerves. Can also affect myelin-covered gray matter om CNS.thus is can affect brainstem, cerebellum, cerebral hemispheres, and spinal cord.
• Easily misdiagnosed as psychogenic disturbance or conversion disorder.
• Visual disturbances, motor, fatigue, weakness, spasms, loss of sphincter control, dysarthriaDiagnosis made if $2$ or more attacks and objective evidence of lesions in at least $2$ areas of CNS.
• Course is unpredictable. Can go into remission, few attacks, or slow accumulation of deficits.
• Gait disturbances, visual deficit, cerebellar dysfunction, trigeminal neuralgia, Bell's palsy, and facial myokymia (involuntary, repetitive eyelid spasms), cognitive deficits, aphasia and apraxia of speech, and dysphagia. More symptoms if MS progresses more rapidly.
• Dysarthria usually not presenting symptom, but it can be in $25\%$.
• Dysarthria can be any single or combo type of dysarthria. Spastic-ataxic is most common. Usually minimal to mild.

Toxic Metabolic Conditions

• Wilson's Disease: Autosomal recessive genetic metabolic disorder due to inappropriate processing of dietary copper.
  • Leads to a build-up of copper in the liver; the presence of copper-like ring discoloration of the eyes, also called sunflower cataract, confirms the condition; and copper in the brain.
  • Emerges late adolescence or early adulthood, even into 70's. Can be fatal if misdiagnosed.
  • Initial presentation usually dystonia, parkinsonism, and ataxia, but also liver failure or psychiatric disturbances. Pathognomonic sign: golden brown ring around the cornea of the eyes reflecting copper deposits.
  • Classic signs: wing-beating tremor when the arms are outstretched, with dysarthria, dystonia, a stiff vacuous smile, and other signs of parkinsonism. Basal ganglia most severely affected.
  • Low copper diet, zinc to reduce copper absorption and meds to improve urinary excretion of copper can control copper balance and improve neuro function.
  • Dysarthria is a cardinal feature. May be initial symptom. Most common: hypokinetic, spastic, and ataxic.
• Manganese Toxicity:
  • Chronic manganese poisoning causes basal ganglia toxicity.
  • Occupational exposure, chronic liver disease, illicit drug abuse.
  • Mixed hypokinetic (dystonic)-hypokinetic dysarthria noted to occur after 6-12 months of IV use of ephedrone, an amphetamine-like drug.
• Hypoxic Encephalopathy:
  • Diffuse neurologic condition due to lack of oxygen to the brain because of heart or circulatory failure, or respiratory failure.
  • Cause usually is MI, carbon monoxide poisoning, suffocation, diseases that paralyze respiratory muscles (Guillian- Barre) or diffuse CNS damage secondary to trauma,
  • If oxygen deprevation lasts several minutes, permanent neuro damage occurs.
  • If consciousness and responsiveness returns, most common deficits involve memory, personality, poor insight, visuospatial problems, spasticity, ataxia, dystonia, parkinsonism, tremor, action myoclonus, and pseudobulbar palsy.
  • Involvement of cortical, extrapyramidal, and cerebellar structures predict single occurences or combos of hypokinetic, hyperkinetic, and ataxic forms.
• Osmotic Demyelination Syndrome (Central Pontine and Extrapontine Myelinolysis):
  • Metabolic disease damaging the brain's myelin.
  • CPM: pontine matter
  • EPM: areas beyond the pons
  • Can be associated with alcoholism, liver transplantation, and rapid rise in serum sodium concentration, renal failure.
  • Most common is rapid correction of hyponatremia (low sodium in blood)
  • Present with seizures followed by decline with dysarthria, dsyphagia, oculomotor problems and quadraplegia.
  • Dysarthria is presenting symptom in $30\%$ of cases. ss, ataxic, and hyperkinetic singly or in combo.
  • With quick diagnosis and intensive care treatment, about $25\%$ have good, functional recovery, but persistent disability and death are not uncommon.
• Hepatocerebral Degeneration:
  • Can occur in survivors of hepatic coma or in people with chronic liver disease.
  • Common clinical signs: limb tremor, chorea or choreoathetosis, unsteady gait, ataxia, and dysarthria.
  • Corticospinal signs and cognitive deficits may be present.
  • Possible dysarthrias: hypokinetic, hyperkinetic, spastic, or ataxic.

Trauma, Neoplasm, Infectious and Autoimmune Diseases

• Trauma: Diffuse or focal lesions due to TBI or closed head injury can produce any form of dysarthria. Lesions were in subcortical areas and posterior fossa; surgical trauma can result in mixed dysarthrias.
• Neoplasm: Tumors, particularly brainstem, can cause mixed dysarthria due to mass effect or invasion of brainstem or other CNS tissue. Brainstem tumors are associated with combos of spastic, ataxic, and/or flaccid dysarthria.
• Infectious and Autoimmune Diseases: Meningitis, encephalitis, and AIDS can be associated with mixed dysarthrias, causing diffuse or multifocal areas of damage.

Duffy Words of Wisdom

• It is not always clear-cut to delineate the various dysarthrias; uncertainty abounds.
• You may feel certain about one of the components but not all.
• Uncertainty arises due to overlapping manifestations of diseases, shortcomings of perceptual methods, or the