When the word doesn't come out: A synthetic overview of dysarthria

    When the word doesn’t come out a synthetic overview of dysarthria Liborio Rampello, Luigi Rampello, Francesco Patti, Mario Zappia PII: DOI: Reference:

S0022-510X(16)30539-1 doi: 10.1016/j.jns.2016.08.048 JNS 14778

To appear in:

Journal of the Neurological Sciences

Received date: Revised date: Accepted date:

30 March 2016 30 July 2016 22 August 2016

Please cite this article as: Liborio Rampello, Luigi Rampello, Francesco Patti, Mario Zappia, When the word doesn’t come out a synthetic overview of dysarthria, Journal of the Neurological Sciences (2016), doi: 10.1016/j.jns.2016.08.048

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When the word doesn't come out

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A synthetic overview of dysarthria

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Liborio Rampello, Luigi Rampello, Francesco Patti, Mario Zappia

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GF Ingrassia Department, Neurosciences Section, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy

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Correspondence to: Liborio Rampello Dipartimento GF Ingrassia, Sezione di Neuroscienze, Università degli Studi di Catania, Via Santa Sofia 78, 95123, Catania, Italy. Tel. and fax: 0039-095 3782622 E-mail: [email protected]

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Motor speech disorders are common in a number of neurological conditions including diseases involving impairment of the pyramidal, extrapyramidal, and cerebellar pathways, cranial nerves, muscular apparatus, neuromuscular plaque, and of cognitive, symbolic and mnestic activities. The diagnosis of speech disorders, namely the dysarthrias, involves the assessment of characteristic structural cerebral, prosodic, phonetic and phonemic changes, often flanked by concomitant functional, clinical, neuroradiological, neurophysiological and behavioral impairment. This paper presents a brief outline of the most significant associations to facilitate prompt differential diagnosis and thereby reduce the number of instrumental examinations required for diagnostic testing.

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Keywords: dysarthria, anarthria, apraxia of speech, speech production, motor speech disorders

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1. Introduction

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Language represents cortico-cortical and cortico-subcortical network activity. Speech is a complex process that relies on the functional integrity of the central and peripheral nervous system, cranial nerves and the muscles involved in speech production, in addition to good lung and pharyngeal (vocal cords) function. Plainly, speech also requires the interrelated systems of cognition and perception (auditory and visual word processing) to be intact, bearing in mind the individual and interindividual variability of these mechanisms. 2. Speech production

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Given the complex mechanisms underlying speech production, speech should probably be considered the expression of a global integrated response of the human brain, but some nervous system structures certainly play a crucial functional role. Correct speech production has been widely investigated and extensively revised: the auditory processing common to speech and nonspeech sounds, speech selective auditory responses (= phonological processing), speech comprehension, speech production, covert and overt articulatory planning, and auditory motor feedback during speech production have been updated by an in-depth highly illustrated overview on the identification of multiple brain areas with functional neuroimaging techniques such as positron emission tomography, functional magnetic resonance imaging and techniques such as magnetoencephalography and electroencephalography [1]. Because of the complexity of speech pathophysiology of the speech, the functional role of each region is only partially known. A special role is attributed to the anterior and posterior temporal areas, ventral inferior frontal areas, dorsal superior frontal gyrus, and the angular gyri, increasingly involved in speech comprehension. The processing involved in speech production overlaps that involved in speech comprehension, because the two involve the same neural structures [2]. Speech function is no longer the exclusive preserve of Broca's and Wernicke's centers, and the cerebellum is now acknowledged to play a major role in word generation [3,4], while the basal temporal language area, anterior cingulate and left inferior prefrontal cortex are involved in a range of different language tasks [5]. Speech production involves more than sensorimotor activity in the pre- and post-central regions controlling the orofacial muscles. It also involves laryngeal activity, phonation and the voluntary control of breathing. A 2

ACCEPTED MANUSCRIPT distinction should also be made between areas involved in motor execution and the cerebellum and subcortical areas involved in the timing and control of motor activity [1]. The effect of aging on the neural correlates of phonological word retrieval has been evaluated by Geva et al. [6].

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2.1 Evaluation of speech characteristics

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Speech production involves respiration, phonation, articulation and prosody. Speech is assessed via a combination of perceptual, acoustic and other instrumental methods. Voice and language quality can be variously evaluated with different methods reported in the literature and employed in several scientific fields. Quality measurement methods must be objective, reliable, valid, and sensitive [7]. “ Intelligibility is only one specific attributes of the perceived integral speech quality. Even if modern transmission systems make the far-end speaker almost perfectly intelligible, specific speech processing systems such as hearing aids are still evaluated through intelligibility experiments. In such tests, the subject is asked to rewrite the understood parts of the listened speech sample. The output score then corresponds to a percentage of correct recognition”. The auditory and instrumental measurement methods dedicated to assessments of perceived speech quality have been described by Côté [7]. Acoustic analysis can be a valuable complement to perceptual evaluation of dysarthric speech. Several literature reports have discussed the main types of acoustic analysis available for the study of speech, specifying the components needed for a modern speech analysis laboratory, including equipment for recording and analysis, and listing possible measurements for various aspects of phonation, articulation and resonance, manifesting in neurologically disordered speech [8-10] A promising assessment tool is multi-parameter acoustic analysis, such as the MultiDimensional Voice Program for the dysarthria associated with Parkinson disease (PD), cerebellar disease, amyotrophic lateral sclerosis (ALS), traumatic brain injury, unilateral hemispheric stroke, and essential tremor [11]. In addition to acoustic and perceptual methods, aerodynamic and endoscopic imaging techniques are used for a complete voice assessment [12-14]. The clinical application of mechanical interruption methods for measuring aerodynamic parameters with the airflow interrupter have yielded interesting data and defined the major advances in laryngeal aerodynamics research [15,16]. 2.2 Apraxia of speech Damage to structures involved in speech planning and programming result in apraxia of speech (AOS), with or without nonverbal orofacial apraxia. Orofacial or buccofacial apraxia is due to lesions to the frontal and central (rolandic) opercula, adjacent portions of the first temporal convolution and the anterior portion of the insula. Clinical features include disturbances in purposeful learned movement of the oral/respiratory structures despite intact strength of peripheral speech musculature [17]. AOS is classically attributed to lesions to Broca’s area, the premotor and supplementary motor areas of the frontal lobe of the dominant hemisphere, the parietal lobe of somatosensory cortex, supramarginal gyrus and insula. The core deficit of AOS is an articulatory disorder marked by difficulty in programming the positioning of the speech muscles and sequencing the muscle movements for volitional production of phonemes [1720]. This occurs in the absence of aphasia or dysarthria, in which the precision and consistency of movements underlying speech are impaired without neuromuscular deficits. AOS is not associated with weakness, paralysis of speech musculature, or difficulty with involuntary motor control for chewing or swallowing, but involves distorted sound substitutions or additions, separation of syllables, omissions, additions, repetitions, 3

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substitutions of speech, lengthened vowel and/or consonant segment, syllable segmentation across words [21].The exact brain regions associated with AOS are still a matter of debate. Recent data have pointed to the crucial role of the left precentral gyrus associated with AOS in acute to subacute stroke patients, suggesting a role of this brain region in motor speech production [21]. AOS or progressive AOS (PAOS) can occur in neurodegenerative disease, and beta-amyloid (Aβ) deposition can be observed in primary AOS and PAOS, heralding neurodegenerative disease, most often progressive supranuclear palsy or corticobasal degeneration. The clinical features of PAOS are caused by lesions in the premotor and supplementary motor areas of the frontal lobe. Unlike stroke-induced AOS, where damage to the left precentral gyrus is associated with AOS in acute stroke, PAOS injury does not have a vascular distribution, and its onset is slowly progressive rather than acute [22-25]. 3. Aphasia

4. The dysarthias

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Neurological diseases are customarily defined by hallmark symptoms and signs also identified with the aid of instrumental tests to establish the aetiopathogenesis and hence the appropriate treatment. Symptoms may affect language that can be impaired or lost in different ways, thereby helping to characterize the condition. Motor speech disorders are divided into two major categories: the aphasias and the dysarthrias. Aphasia is a failure of lexical-semantic or syntactic processing, a disturbance of language that can affect speech, comprehension of speech, reading, and writing. The condition may disrupt the syllable repetitions required to produce phonemes, with elisions or syllable transpositions resulting in so-called neologistic jargon aphasia that makes speech difficult or impossible to understand. This type of aphasia, known as motor aphasia, can also be associated with a disturbed comprehension of other people’s speech as if it were an incomprehensible foreign language. This type of aphasia is called sensory aphasia. The two forms of aphasia are frequently accompanied by similar writing disorders, motor aphasia affecting writing expression and sensory aphasia affecting comprehension of speech. In the severest cases, both types of aphasia may coexist (sensory-motor aphasia) depriving patients of the ability to communicate with a severe impact on relationships.

Whereas the aphasias are caused by cortical lesions, other language disorders, the dysarthrias, are due to pathological processes involving the subcortical structures. The dysarthrias constitute a set of disorders affecting speech with no changes to comprehension of writing or language, changes in the grammatical construction of words and sentences or cognitive disorders. This group of language disorders reflects only neuromuscular disturbances of strength, speed, tone, steadiness or accuracy of the movements responsible for speech production. They are named according to the etiology of the lesion responsible with the term anarthria used for rare cases of total speech loss [26]. 4.1 Nosological correlates of dysarthria This category of speech disorders comprises a series of neurological features that depend on the different locations, levels and severity of neuromuscular disturbances resulting in various degrees of speech impairment despite the correct programming of verbal sequences. The dysarthrias are caused by subcortical lesions and hence do not affect a patient’s symbolic or mental functions, or the ability to read, write and understand other people’s speech. Subcortical dysfunction depends on the lesion locus and etiology, resulting in specific phenotypes reflecting the pathogenesis of the illness. Speech is made possible by the correct 4

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coordinated actions of a series of functions and structures. In particular, the cerebral cortex must be linked to the motor nuclei of cranial nerves V, VII, IX, X and XII and the phrenic nerve. Also essential is the integrity of the cerebellum and basal ganglia and good expiratory and ventilatory function to ensure a continuous flow of air during speech, a correct articulation of syllables, consonants and vowels, and motility of the pharynx, vocal cords, soft palate, tongue and lips. Any alteration to any of these districts will inevitably give rise to typical speech changes depending the lesional site. Hence it is necessary to listen to the patient’s spontaneous speech and possibly have him/her read a text to disclose any changes in speech articulation, tone of voice, pronunciation, prosody, rhythm, continuity, intelligibility, verbal tone and fluency [18, 27]. Different forms of dysarthria are also encountered in the same neurological condition and sometimes in the same individual, with inter and intra-individual variability as in the case of Parkinson’s disease when patients may present bradylalia (very slow speech), hypophonia (weak voice reduced to voice loss), tachyphemia (rapid speech accelerated to the point of syllabic conglutination and hence quite unintelligible), monotonous voice (speech lacking emotional inflection and normal prosodic tone), brady/tachyphemia (speech delay with fluctuating speaking rate in the same sentence): language disorders accompanying various changes in motor behavior (hypo-akinesia, hyperkinesia, festination) (Table 1).

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Speech change Motor change ______________________________________________________ Bradylalia Hypokinesia Hypophonia/aphonia Hypokinesia/akinesia Monotonous voice Hypokinesia Tachyphemia Festination Brady-tachyphemia Dyskinesias ______________________________________________________ Table 1- Possible motor speech changes in Parkinson’s disease

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The major categories of dysarthria include: 1. Spastic or pyramidal dysarthria 2. Extrapyramidal or rigid dysarthria 3. Ataxic or cerebellar dysarthria 4. Neuromuscular dysarthria (flaccid dysarthria ) 5. Hypophonia 6. Tremulous voice 7. Stuttering 4.2 Spastic dysarthria Spastic dysarthria is caused by bilateral lesions affecting the corticobulbar pathways to the cranial nerve nuclei involved in speech. As these bilateral projections stem from both motor cortices, the lesions must be bilateral to result in stable dysarthria: this is the case of multiple or recurrent strokes in the setting of multi-infarct encephalopathy, demyelinating lesions or central lesions due to amyotrophic lateral sclerosis. This type of dysarthria is also known as pseudobulbar dysarthria to distinguish it from bulbar dysarthria in which paralysis caused by lesions to the nuclei or cranial nerves is associated with signs of motor neuron disease (atrophy and fasciculations). These signs are lacking in spastic dysarthria, which may be associated with symptoms typical of a pseudobulbar or epibulbar syndrome due to the extensive bilateral corticobulbar lesions: laughter and crying spasticity (for no apparent 5

ACCEPTED MANUSCRIPT reason or due to loss of emotional control), osteotendinous hyperreflectivity in all four limbs, inversion of the plantar reflex (Babinski sign), dysphagia, loss of sphincter control, small stepping gait [28]. Bulbar and pseudobulbar dysarthria may coexist in certain forms of amyotrophic lateral sclerosis, constituting its pathognomonic hallmark [29].

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4.3 Extrapyramidal dysarthria

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Dysarthria is common in both hypo/hyperkinetic extrapyramidal disorders. This is particularly true in Parkinson’s disease in which the dysarthria presents interindividual and sometimes intra-individual differences depending on the time of day or disease stage. The most common disorder is slow speech when progressive loss of fluency is associated with progressively slowed limb movements and kinetic gait reflecting a general hypokinesia (dressing, personal hygiene, diet). The other main feature characterizing extrapyramidal dysarthria is the low vocal pitch due to the onset of a typical hypophonia that may evolve into total aphonia. In these cases no words can be heard even when the examiner puts his ear to the patient’s mouth. More commonly, vocal tone is reduced but perceptible due to a weak voice. Another characteristic feature almost always present is the loss of prosody with a prevalently monotonous apparently apathetic tone of voice detached from the emotional content of the verbal expressions, in tandem with patient’s reduced facial expression. Contrary to appearances, patients’ emotions of patients are generally maintained, except in cases of concomitant mood depression that may accompany, follow or even precede the motor symptoms (as noted and described some 100 years ago). Some patients also present palilalia, the abnormal repetition of syllables, words or phrases. Speech may sometimes be hampered by abundant salivation leading to drooling in Parkinsonian patients. However, speech is not always slowed and some patients present the opposite disorder with phonemes pronounced so fast that they are unintelligible. This appears to be the result of syllabic conglutination reflecting the corresponding motor impairment known as festination making speech sound like an unintelligible grunting sound. Some of these changes are also seen in other forms of degenerative Parkinsonism like progressive supranuclear palsy [30]. Treatment of extrapyramidal motor symptoms may often be accompanied by an improvement in the dysarthria. Sometimes mood depression can also lead to motor slowing, bradyphrenia, hypophonia and bradylalia (so-called pseudodementia), which usually respond to adequate antidepressant treatment [31,32]. Different changes have been observed in hyperkinetic extrapyramidal disorders like chorea and in myoclonus, clinical conditions characterized by an increase in vocal tone with possible loss of verbal fluency due to unexpected phonemic hiatus and tonal variations in pronouncing the same word, resulting in typically jerky and explosive articulation. This reduced verbal fluency is sometimes the result of the random onset of characteristic hyperkinesias shared by both of these clinical conditions. Also included in this group of speech disorders are the typical tic syndromes, the most severe being Gilles de la Tourette syndrome with its characteristic repetitive verbal tics accompanied by motor and in rare cases coprolalia [33]. 4.4 Cerebellar dysarthria Acute and chronic, hereditary or acquired cerebellar disorders are often accompanied by cerebellar dysarthria, especially in patients with lesions in the left paravermian region. These disorders typically result in slow speech with difficulty pronouncing words and scanning syllables often pronounced in a high-pitched voice thereby reducing speech fluency. This is typically found in the best-known cerebellar dysfunction in multiple sclerosis (MS), as 6

ACCEPTED MANUSCRIPT described by Charcot who included scanning speech in the triad of symptoms characterizing the disease. A variation in speech tone sometimes also affects pronunciation of the same word leading to “explosive speech” [34,35]. 4.5 Neuromuscular dysarthria

Primary muscular atrophy Muscle disorders (oculopharyngeal or facioscapulohumeral dystrophy, myositis or myotonia) 3. Motor neuron disease (like ALS, especially the progressive bulbar palsy variant) 4. Temporary facial paralysis (as in acute polyradiculoneuropathy or Bell’s palsy) 5. Neuromuscular plaque disorders (like myasthenia) 6. Syringobulbia 7. Isolated or multiple paresis of cranial nerves V, VII, IX, X, XII (Garcin or Guillain-Barré-Strohl syndrome, cancer) Table 2 Neuromuscular dysarthria

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Any neuromuscular impairment can alter the quality of speech, especially when the motor functions of the pharynx, larynx, soft palate, facial and lingual musculature are lost. This typically occurs in all diseases involving injury to the lower motor neurons originating in the bulbar or lower pontine regions (such as spinal muscular atrophy), muscle disorders (like oculopharyngeal or facioscapulohumeral dystrophy, myositis or myotonia), motor neuron disease (like amyotrophic lateral sclerosis (ALS), especially the progressive bulbar palsy variant), neuromuscular plaque disorders (like myasthenia), transient facial paralysis (as in acute polyradiculoneuropathy), lacunar pontine ischaemic stroke (with concomitant dysarthria, dysphagia, facial paresis and changes in the fine motility of the hand), syringobulbia, and all conditions of isolated or multiple paresis of cranial nerves V, VII, IX, X, XII, whose speech disorder is known as bulbar dysarthria, in which patients talk as if they had food in their mouths. Obviously, the type of alteration is closely linked to the locus and extent of the lesion and any concomitant dysphagia and hypersalivation in the oral cavity is responsible for further speech impairment. Vocal cord paralysis will lead to hoarseness while mono- or bilateral paralysis of the labial musculature will impair the articulation of labial consonants (p and b). Lingual paralysis will limit the pronunciation of the letters r and l (as in ALS), while paralysis of the soft palate will give speech a characteristic nasal tone as in myasthenia. Neuromuscular dysarthria is characterized by muscular hypotrophy of the lips, cheeks and/or tongue possibly with typical fasciculations in chronic denervation syndromes. The search for the typical electromyographic stigmata of spontaneous activity (positive waves, fibrillations and fasciculations) will identify acute lesions [36] (Table 2).

4.6 Neuroanatomical correlates of dysarthria 1.  

Cortical lesions (cortical dysarthria): lesion of the lower portion of the precentral gyrus (stroke, tumor) frontal dysarthria (traumatic injury, late complications of syphilis)

2. Bilateral lesions of the corticobulbar pathways typically observed in epibulbar or pseudobulbar syndromes as in bilateral cerebrovasculopathies, with difficulty in sound production and articulation (spastic dysarthria);

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ACCEPTED MANUSCRIPT 3. Basal ganglia lesions, such as those to the caudate nucleus and putamen, associated with involuntary movements interrupting phonation as in chorea (hyperkinetic dysarthria), the substantia nigra pars compacta or nucleus pallidus, associated with rigidity, hypertonus, hypokinesia, and tremor, causing monotone voice, breath voice, and slow speech as in Parkinson’s disease (hypokinetic dysarthria);

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4. Cerebellar lesions (lateral hemispheres or vermis) associated with ataxia and imbalance of the orofacial or buccofacial musculature, with irregular sound emission resulting in scanning speech (as in MS) or voice tremor (as in essential tremor) (ataxic dysarthria);

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5. Bilateral lesions of the cranial nerves (V, VII, IX, X, XII) or lesions of the II motor neurons that innervate speech muscles, including the diaphragm and the intercostal muscles accompanying flaccid dysarthria;  Muscle weakness or poor control of the muscles involved in articulation, such as buccolinguofacial muscle deficit caused by damage to the nuclei or axons of cranial nerves V, VII and XII with defective articulation of consonants (p, b, t, l), as in Guillain-Barré syndrome [37] or spinal and bulbar muscular atrophy (Kennedy’s disease), with possible muscle atrophy and fibrillation, fasciculations, positive sharp waves, and dysphagia [38];  Laryngeal and velopharyngeal deficits with nasal speech due to IX and X cranial nerve injury, with dysphonia, hoarseness and voice impairment [39]; Mixed dysarthria, due to central and peripheral motor neuron lesions, as in ALS;

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Dysarthria caused by neuromuscular junction disease [40-44];

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Dysarthria caused by muscular or mitochondrial disease [45-53].

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4.7 Anarthria

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Central and/or peripheral disturbances lacking verbal expression are known as dysarthria or anarthria (the most severe form of dysarthria). Pure anarthria is the loss of speech sparing writing skills and oral and reading comprehension. It is usually caused by injury to the cortico-subcortical white matter of the dominant hemisphere. Anarthria has been described in association with different lesions: with rapid onset in cases of bulbar onset ALS [54], with opercular syndrome (known as Foix-Chavany-Marie syndrome), a paralysis of the facial, pharyngeal, masticatory, tongue, laryngeal and brachial muscles. It may also be a rare cortical form of pseudobulbar palsies caused by vascular insults to bilateral operculum [55], after ischemic stroke of the pyramidal decussation causing quadriplegia and anarthria [56], as slowly progressive anarthria with late anterior opercular syndrome [57], and as persistent anarthria following mirror infarction in the anterior choroidal artery territory [58]. In an attempt to depict the roles of central and peripheral structures responsible for speech planning and expression, speech can be likened to a boat: specific areas of the cerebral cortex resemble a boat (= words) builder who chooses the characteristics (type, structure, size, shape) required for a specific task such as floating and transport (specific word message). Damage to these areas will result in aphasia or apraxia of speech (no or inadequate speech production). The river bed and the water carrying the boat are like word vectors (speech), both the corticonuclear and corticospinal pathways whose lesions cause anarthria or spastic dysarthria, or the cranial nerves (V, VII, IX, X, XII) whose lesions are responsible for flaccid dysarthria. The basal ganglia represent the weir controlling the flow of water down the river: reduced verbal flow (bradylalia to aphonia as in PD), increased flow (tachyphemia as in PD), or fluctuating flow (stuttering speech as in chorea). The cerebellum can be likened to the navigator controlling the regularity of flow, monitoring the boat’s course trying the avoid 8

ACCEPTED MANUSCRIPT sudden jerks or braking caused by increases or decreases in the boat’s speed, resulting in turbulence and irregular flow. In speech production these verbal flow irregularities are caused by cerebellar control circuit lesions, responsible for changes in aerophonatory parameters, prolonged phonemes and/or intervals, irregular articulation, excessive loudness variations (as in essential tremor, MS or olivopontocerebellar atrophy).

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4.8 Hypophonia

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An abnormally weak voice is commonly observed in all conditions resulting in reduced air flow through the vocal cords, or due to lung diseases or illness leading to respiratory muscle paralysis (myasthenia or Guillain-Barré-Strohl syndrome) or in extrapyramidal disorders, as seen in advanced Parkinson’s disease in which speech becomes a weak whisper. Another fairly common medical condition is hypophonia associated with monotone voice and bradylalia in subjects with major depression.

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4.9 Spasmodic dysphonia

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Spasmodic dysphonia merits a brief mention. This clinical condition, whose etiology remains unsettled, consists in speech altered by a generalized contraction of the phonatory muscles. It is attributed to a form of focal dystonia, like spasmodic torticollis, blepharospasm, and writer’s cramp. It should be borne in mind that major depression, as in the setting of unipolar depression or the depressive stages of bipolar mood disorders, can be responsible for hypophonic and monotonous speech confined to the depressive stage of the illness. 4.10 Aphonia

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Aphonia, or the total inability to produce speech, is found in bilateral vocal cord paralysis, as in the case of bilateral injury to the vagus nerve or functional neuropsychiatric conditions. Unilateral damage to the vagus nerve results in a weak dysphonic voice [59].

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4.11 Tremulous voice

Although tremulous voice is not confined to essential (or familial) tremor, it is its pathognomonic hallmark together with typical head tremor (nodding or shaking) and postural or intentional tremor of the limbs. The condition is familial in around 70% of cases, arising in young adulthood and often with a mild evolution that does not impair speech intelligibility but confers a characteristic tremulous tone to the voice as when air flow through the vocal cords is discontinuous due to expiratory flow impairment [60]. 4.12 Stuttering Stuttering is a speech disorder characterized by a delayed initiation of speech, sudden speech interruption or the repetition of letters or syllables disrupting verbal fluency. A childhood variant, sometimes temporary, has been described with possible familial recurrence, alongside an acquired adult form, sometimes arising during recovery from an aphasic disorder [61, 62]. Stuttering can be tonic or clonic, depending on either the arrested articulation of a syllable or clonic repetition of the same syllable, leading to major speech impairment. In both cases, emotional tension, such as when speaking in public, exacerbates the severity and recurrence of the disorder. Possible reversibility has been described in the acquired adult form implicating the presence of subcortical lesions [63,64]. In the table 3 are shown language features in the most common neurological diseases. 9

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Table 3: >/<, >>/<<, >>>/<<< (mild, medium, strong increment/decrement respectively) 0 = absent Language features in the most common neurological diseases 5. Conclusions Without a doubt, communication is one of the most important functions for the survival and quality of life of human beings. In the animal world, it is also an effective tool among individuals of the same species and even among different species with effective communication skills. Nonetheless, communication reaches its maximum potential in human beings for whom communication symbols combined in an infinite variety of ways yield very high levels of expressivity. 10

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The wealth of human communication is also the result of stylistic and linguistic devices (tone, fluency, inflection, speed, timing). In addition to miming and gestures, these features give human speech myriad combinations that make it specific to individual personalities (as demonstrated in the art world and theater by myriad imitations, caricatures or parodies). Under normal conditions, daily life voice modulations express our mood even without our awareness. In some cases, the sense and message of a verbal expression may even transcend the literal meaning of the words pronounced, saying much more than what is uttered literally (a few words to say a lot and a lot of words to say little or nothing). Communication is effective when the will to communicate is combined with all the necessary cognitive functions, the integrity of the cortical areas involved in speech planning and programming and their corticofugal projections to the cranial nerves and anterior horns of the spinal cord all the way to the effector muscles. This overview outlined the main associations facilitating initial differential diagnosis while a comprehensive diagnosis of the disorder will require the full armamentarium of available tools including neuroradiological, neuropsychological, neurophysiological and, if necessary, neuropathological tests. Careful clinical screening will serve to minimize the number of instrumental examinations required and thereby curb current healthcare expenditure. Conflicts of interest The authors declare that they have no conflicts of interest.

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References

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[1] C.J. Price, A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language and reading, Neuroimage. 62 (2) (2012) 816-847. doi: 10.1016/j.neuroimage.2012.04.062. [2] P. Tremblay, S.L. Small, Motor response selection in overt sentence production: a functional MRI study. Front Psychol. 2 (2011) 253. doi: 10.3389/fpsyg.2011.00253. eCollection 2011. [3] H. Ackermann, D. Wildgruber, W. Grodd, Neuroradiologic activation studies of cerebral organization of language capacities. A review of the literature, Fortschr Neurol Psychiatr. 65(4) (1997) 182-194. [4] P. Mariën, H. Ackermann, M. Adamaszek, et al. Consensus paper: Language and the cerebellum: an ongoing enigma, Cerebellum. 13(3) (2014) 386-410. doi: 10.1007/s12311013-0540-5. [5] H. Chertkow, S. Murtha. PET activation and language. Clin Neurosci. 4(2) (1997) 78-86. [6] S. Geva, P.S. Jones, J.T. Crinion, C.J. Price et al, The effect of aging on the neural correlates of phonological word retrieval, J Cogn Neurosci. 24(11) (2012) 2135-2146. doi: 10.1162/jocn_a_00278. [7] N. Côté, Speech Quality Measurement Methods, Integral and Diagnostic Intrusive Prediction of Speech Quality, 37 T-Labs Series in Telecommunication Services, 1, 2011 doi: 10.1007/978-3-642-18463-5_2. [8] R.D. Kent, G. Weismer, J.F. Kent, H.K. Vorperian, J.R. Duffy, Acoustic studies of dysarthric speech: methods, progress, and potential, J Commun Disord. 32(3) (1999) 141-180. [9] J. Rusz, C. Bonnet, J. Klempíř, et al, Speech disorders reflect differing pathophysiology in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy, J Neurol. 262 (4) (2015) 992-1001. doi: 10.1007/s00415-015-7671-1. [10] J.R. Duffy, E.A. Strand, H. Clark et al, Primary progressive apraxia of speech: clinical features and acoustic and neurologic correlates, Am J Speech Lang Pathol. 24(2) (2015) 88100. doi: 10.1044/2015_AJSLP-14-0174.

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[11] R.D. Kent, H.K. Vorperian, J.F. Kent, J.R. Duffy. Voice dysfunction in dysarthria: application of the Multi-Dimensional Voice Program. J Commun Disord. 36(4) (2003) 281306. [12] D.D. Mehta, R.E. Hillman. Voice assessment: updates on perceptual, acoustic, aerodynamic, and endoscopic imaging methods. Curr Opin Otolaryngol Head Neck Surg. 16(3) ( 2008 ) 211-5. doi: 10.1097/MOO.0b013e3282fe96ce. [13] A. Lowit, A. Kuschmann, K. Kavanagh. Phonological markers of sentence stress in ataxic dysarthria and their relationship to perceptual cues. J Commun Disord. 50 ( 2014 ) 818. doi: 10.1016/j.jcomdis.2014.03.002. [14] P.N. Carding, J.A. Wilson, K. MacKenzie, I.J. Deary. Measuring voice outcomes: state of the science review. J Laryngol Otol. 123(8) (2009) 823-9. doi: 10.1017/S0022215109005398. [15] M.R. Hoffman, A.L. Rieves, K. Surender, E.E. Devine, J.J. Jiang. Evaluation of auditory and visual feedback for airflow interruption. J Voice. 27(2) (2013) 149-54. doi: 10.1016/j.jvoice.2012.10.002. [16] J.J. Jiang, A.L. Maytag. Aerodynamic measures of glottal function: what extra can they tell us and how do they guide management. Curr Opin Otolaryngol Head Neck Surg. 22(6) ( 2014 ) 450-454. doi: 10.1097/MOO.0000000000000107. [17] C. Frattali and J.R. Duffy. Characterizing and assessing speech and language disturbances. In I. Litvan ( ed ) Current Clinical Neurology: Atypical parkinsonian disorders, Humana Press Inc., Totowa, NJ, 2005, pp 255-276 [18] F.L. Darley, AE Aronson, J.R. Brown. Differential diagnostic patterns of dysarthria. J Speech Hear Res. 12(2) (1969 ) 246-269 [19] E. Maas, D.A. Robin, D.L. Wright, K.J. Ballard. Motor programming in apraxia of speech. Brain Lang. 106(2) ( 2008 ) 107-118. doi: 10.1016/j.bandl.2008.03.004. [20] J. Ogar, H. Slama, N. Dronkers, S. Amici, M.L. Gorno-Tempini. Apraxia of speech: an overview. Neurocase. 11(6) ( 2005 ) 427-432. doi: 10.1080/13554790500263529. [21] E.A. Strand , J.R. Duffy , H.M. Clark , K. Josephs The Apraxia of Speech Rating Scale: a tool for diagnosis and description of apraxia of speech J Commun Disord. 51 (2014) 43-50. doi: 10.1016/j.jcomdis.2014.06.008. [22] R. Itabashi, Y. Nishio, Y. Kataoka, et al. Damage to the Left Precentral Gyrus Is Associated With Apraxia of Speech in Acute Stroke. Stroke. 47(1) (2016) 31-36. doi: 10.1161/STROKEAHA.115.010402. [23] J.R. Duffy, K.A. Josephs. The diagnosis and understanding of apraxia of speech: why including neurodegenerative etiologies may be important. J Speech Lang Hear Res. 55(5) ( 2012 ) S1518-S1522. doi: 10.1044/1092-4388(2012/11-0309). [24] W. Ziegler, I. Aichert, A. Staiger. Apraxia of speech: concepts and controversies. J Speech Lang Hear Res. 55(5) ( 2012 ) S1485-S1501. doi: 10.1044/1092-4388(2012/12-0128. [25] H. Botha, J.R Duffy, J.L. Whitwell, et al. Classification and clinicoradiologic features of primary progressive aphasia (PPA) and apraxia of speech. Cortex. 69 ( 2015 ) 220-236. doi: 10.1016/j.cortex.2015.05.013. [26] J.R. Duffy. Motor speech disorders: clues to neurologic diagnosis. In Adler CH, Ahlskog JE. (Eds). Parkinson’s Disease and Movement Disorders: Diagnosis and Treatment Guidelines for the Practising Physician.Rochester, MN Mayo Foundation for Medication and Research, 496 (2000) pp 35-53. [27] P.D. Neilson, N.J. O’Dwyer. Pathophysiology of dysarthria in cerebral palsy. J Neurol Neurosurg Psychiatry. 44 (1981) 1013-1019. [28] L. Rampello, A. Alvano, G. Battaglia, et al. Different clinical and evolutional patterns in late idiopathic and vascular parkinsonism. J Neurol. 252(9) (2005) 1045-1049. [29] S.P. Ringel, J.R. Murphy, M.K. Alderson, W. Bryan et al. The natural history of amyotrophic lateral sclerosis. Neurology. 43(7) (1993) 316-322.

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[30] L. Rampello, V. Buttà, R. Raffaele, et al. Progressive supranuclear palsy: a systematic review. Neurobiol Dis. 20(2) ( 2005 ) 179-186. [31] L. Rampello, S. Chiechio, R. Raffaele, et al. The SSRI, citalopram, improves bradykinesia in patients with Parkinson's disease treated with L-dopa. Clin Neuropharmacol, 25(1) (2002) 21-24. [32] L. Rampello, F. Nicoletti, F. Nicoletti. Dopamine and depression: Therapeutic implications. CNS Drugs, 13(1) (2000) 35-45. [33] J. Jankovic. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. Review 79(4) (2008) 368-376. doi: 10.1136/jnnp.2007.131045. [34] R. Lechtenberg, S. Gilman. Speech disorders in cerebellar disease. Ann Neurol. 3 (1978) 285-290. [35] L. Rampello, B. Casolla, L.,Rampello et al. The conditioned eyeblink reflex: a potential tool for the detection of cerebellar dysfunction in multiple sclerosis. Mult. Scler. 17(10) (2011) 1155-1161 doi: 10.1177/1352458511406311. [36] Continuum: Lifelong Learning in Neurology: Disorders of Speech and Language 5 (2) 1999 pp 27-40. [37] R.K. Lyu, S.T. Chen. Acute multiple cranial neuropathy: a variant of Guillain-Barré syndrome? Muscle Nerve. 30(4) (2004) 433-436. [38] N. Atsuta, H. Watanabe, M. Ito, et al. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain. 129( 6) (2006) 1446-1455. [39] J.D. England, A.K. Asbury. Peripheral neuropathy. Lancet. 363(9427) (2004) 21512161. [40] T.M. Burns, J.A. Russell, D.H. La Chance, H.R. Jones. Oculobulbar involvement is typical with Lambert-Eaton myasthenic syndrome. Ann Neurol. 53(2) (2003) 270-273. [41] R.F. Robinson, M.C. Nahata. Management of botulism. Ann Pharmacother. 37(1) ( 2003 ) 127-131. [42] J.P. Bouwyn, P. Magnier, A.L. Bédat-Millet et el. Anti-MuSK myasthenia gravis with prolonged remission. Neuromuscul Disord. 26(7) (2016) 453-454. doi: 10.1016/j.nmd.2016.04.008. [43] K.J. Kluin, M.B. Bromberg, E.L. Feldman, Z. Simmons. Dysphagia in elderly men with myasthenia gravis. J Neurol Sci. 138(1-2) ( 1996 ) 49-52. [44] M. Migliore, G. Alongi, L. Rampello, M. Astuto. Video assisted trans-cervical thymectomy. A minimally invasive approach to treat non-thymomatous myasthenia gravis. Ann Ital Chir. 84(6) (2013) 667-670. [45] B.J. de Swart, B.G. van Engelen, J.P. van de Kerkhof, B.A. Maassen. Myotonia and flaccid dysarthria in patients with adult onset myotonic dystrophy. J Neurol Neurosurg Psychiatry. 75(10) (2004) 1480-1482. [46] T. Chen, C. Pu, Q. Shi, et al. Chronic progressive external ophthalmoplegia with inflammatory myopathy. Int J Clin Exp Pathol. 7(12) (2014) 8887-8892. [47] H.N. Jones, K.D. Crisp, P. Asrani, R. Sloane, P.S. Kishnani. Quantitative assessment of lingual strength in late-onset Pompe disease Muscle Nerve. 51(5) (2015) 731-735. doi: 10.1002/mus.24523. [48] M.D. Meyerson, E. Lewis, K. Ill. Facioscapulohumeral muscular dystrophy and accompanying hearing loss. Arch Otolaryngol. 110(4) (1984) 261-266. [49] S. Rajakulendran, R.D. Pitceathly, J.W. Taanman, et al. Clinical, Neuropathological and Genetic Study of Homozygous A467T POLG-Related Mitochondrial Disease. PLoS One. 11(1) (2016) e0145500. doi: 10.1371/journal.pone.0145500. [50] A. Reyes, L. Melchionda, A. Nasca, et al. RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy. Am J Hum Genet. 97(1) (2015) 186-93. doi: 10.1016/j.ajhg.2015.05.013..

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[51] J. Altmann, B. Büchner, A. Nadaj-Pakleza et al. Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: data from the German mitoNET registry. J Neurol. 263(5) ( 2016 ) 961-972. doi: 10.1007/s00415-016-8086-3. [52] F. Hanisch, M.Kornhuber, C.L. Alston, et al. SANDO syndrome in a cohort of 107 patients with CPEO and mitochondrial DNA deletions. J Neurol Neurosurg Psychiatry. 86(6) (2015) 630-634. doi: 10.1136/jnnp-2013-306748. [53] V.C. Neeve, D.C. Samuels, L.A. Bindoff et al. What is influencing the phenotype of the common homozygous polymerase-γ mutation p.Ala467Thr? Brain. 135(Pt 12) (2012) 36143626. doi: 10.1093/brain/aws298. [54] M.R. Turner, J. Scaber, J.A. Goodfellow, et al. The diagnostic pathway and prognosis in bulbar-onset amyotrophic lateral sclerosis. J Neurol Sci. 294 (1-2) (2010) 81-85. doi: 10.1016/j.jns.2010.03.028. [55] A. Milanlioglu, M.N. Aydın, A. Gökgül, et al. Ischemic bilateral opercular syndrome. Case Rep Med. 2013 513572 (2013). doi: 10.1155/2013/513572. [56] E.G. Wilkins, H. Kamel, E.C. Johnson, et al. Ischemic stroke of the pyramidal decussation causing quadriplegia and anarthria. J Stroke Cerebrovasc Dis. 21(7) (2012) 620.e 1-2. doi: 10.1016/j.jstrokecerebrovasdis.2011.02.001. [57 ] E. Broussolle, S. Bakchine, M. Tommasi, et al. Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes. Neurol Sci. 144(1-2) (1996) 44-58. [58] M. Boes, H. Urbach, T. Klockgether, U. Schlegel. Persistent anarthria following mirror infarction in the anterior choroidal artery territory. Eur J Neurol. 14(4) (2007) e6. doi: 10.1111/j.1468-1331.2006.01658.x. [59] M. Kronenbuerger, J. Konczak, W. Ziegler, et al. Balance and motor speech impairment in essential tremor. Cerebellum. 8 (3) (2009) 389-398 doi: 10.1007/s12311-009-0111-y. [60] H. Ackermann, W. Ziegler. Cerebellar voice tremor. J Neurol Neurosurg Psychiatry. 54 (1991) 74-76. [61] N.A Helm., R.B. Butler and D.F. Benson Acquired stuttering. Neurology. 28 (11) (1978) 1159-1165. [62] J. Rosenbek, B. Messert, M. Collins, R.T. Wertz Stuttering following brain damage. Brain Lang. 6 (1978) 82–96. [63] P.A. Alm. Stuttering in relation to anxiety, temperament, and personality: review and analysis with focus on causality. J Fluency Disord. 40 (2014) 5-21 doi: 10.1016/j.jfludis.2014.01.004. [64] A. Craig-McQuaide, H. Akram, L. Zrinzo, E. Tripoliti. A review of brain circuitries involved in stuttering. Front. Hum. Neurosci. Review article, 8 (884) (2014) 1-20 doi: 10.3389/fnhum.2014.00884.

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Speech change Motor change ______________________________________________________ Bradylalia Hypokinesia Hypophonia/aphonia Hypokinesia/akinesia Monotonous voice Hypokinesia Tachyphemia Festination Brady-tachyphemia Dyskinesias ______________________________________________________ Table 1- Possible motor speech changes in Parkinson’s disease:

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ACCEPTED MANUSCRIPT Primary muscular atrophy Muscle disorders (oculopharyngeal or facioscapulohumeral dystrophy, myositis or myotonia) 10. Motor neuron disease (like ALS, especially the progressive bulbar palsy variant) 11. Temporary facial paralysis (as in acute polyradiculoneuropathy or Bell’s palsy) 12. Neuromuscular plaque disorders (like myasthenia) 13. Syringobulbia 14. Isolated or multiple paresis of cranial nerves V, VII, IX, X, XII (Garcin or Guillain-Barré-Strohl syndrome, cancer) Table 2 Neuromuscular dysarthria

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Table 3: >/<, >>/<<, >>>/<<< (mild, medium, strong increment/decrement respectively) 0 = absent Language features in the most common neurological diseases

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ACCEPTED MANUSCRIPT Highlights Motor speech disorders are common in a number of neurological conditions Aphasia, apraxia of speech, anarthria and different dysarthrias are considered Cortical-subcortical and neuromuscular lesions characterize various dysarthrias Neuroanatomical and nosological correlates can facilitate a prompt differential diagnosis 5. This overview may reduce the number of instrumental examinations required for diagnosis

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1. 2. 3. 4.

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