US20140163070A1

US20140163070A1 - Treatment for cerebral palsy impaired speech in children

Info

Publication number: US20140163070A1
Application number: US14/182,332
Authority: US
Inventors: Bruce Roseman; Gilla Kaplan
Original assignee: Individual
Current assignee: GILROSE PHARMACEUTICALS LLC
Priority date: 2012-05-17
Filing date: 2014-02-18
Publication date: 2014-06-12
Also published as: US20140357668A1; US20160101095A1; US20160030411A1; US9408838B2; WO2015061125A1; US20140357667A1; US9333198B2; US20150320734A1; US9155502B2; US9307942B2; US9161718B2

Abstract

Cerebral palsy impaired speech in children and adolescents are effectively treated by administration of a psychostimulant. Low doses of the psychostimulant significantly (p=0.0025) increases the percentage of correctly pronounced intelligible syllables or words and the ability to more intelligibly communicate (p=0.0309). The improvement in speech persists after cessation of or prior to continued psychostimulant treatment.

Description

PRIOR RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent application Ser. No. 14/059,541, filed Oct. 22, 2013, and claims priority to U.S. patent application Ser. No. 14/059,541, filed Oct. 22, 2013 which is a continuation-in-part of U.S. patent application Ser. No. 14/112,065, filed Oct. 16, 2013, and claims priority to U.S. Ser. No. 14/112,065, filed Oct. 16, 2013 and PCT/US2012/038312, filed May 17, 2012, and to provisional application No. 61/487,847, filed May 19, 2011, which applications are incorporated herein in their entireties by reference thereto.

BACKGROUND OF THE INVENTION

1. Field of the Invention
This invention relates to cerebral palsy impaired speech. This invention also relates to evaluating a subject for and the treatment of speech impairment secondary to cerebral palsy. In one specific aspect, this invention relates to the treatment of cerebral palsy impaired speech in children and adolescents. This invention also relates to speech, language and communication disorders in children diagnosed with cerebral palsy.
2. Background and Discussion of the Art
Cerebral palsy (CP) is a non-progressive disease or disorder involving irreparably damaged or injured areas of the brain, including connections between the cortex and other parts of the brain (the central nervous system) and the muscles (in the peripheral nervous system).
The National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) defines cerebral palsy as any of a number of neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination but do not worsen over time, and then makes clear that cerebral palsy cannot be cured, but treatment will often improve a child's capabilities and that such treatment may include physical and occupational therapy, speech therapy, medications to control seizures, relax muscle spasms, and alleviate pain; surgery to correct anatomical abnormalities or release tight muscles; braces and other orthotic devices; wheelchairs and rolling walkers; and communication aids such as computers with attached voice synthesizers.
There are several causes of cerebral palsy, including maternal trauma or infection resulting in periventricular leukomalacia, genetic mutations resulting in cerebral dysgenesis; fetal stroke resulting intracranial hemorrhage, and hypoxic-ischemic encephalopathy. The several causes of cerebral palsy include complications before birth. Such complications may include genetic mutations, resulting in cerebral dysgenesis, maternal or fetal infections, resulting in encephalomalacia and intra-utero vascular thrombosis (intrauterine strokes). Complications during delivery may result in hypoxic-ischemic encephalopathy. After birth, CP can be the result of non-accidental trauma, encephalitis or meningitis due to any number of infectious or toxic agents.
There are generally three types of cerebral palsy namely (1) ataxic which includes lack of muscle coordination, (2) spastic, which includes tighter muscles and exaggerated reflexes and movements, and (3) dyskinetic movements, which includes slow and uncontrollable withering. Spastic cerebral palsy is further defined as spastic diplegia and spastic quadriplegia.
Dysarthria is one of many speech disorders seen in children with cerebral palsy, resulting from the inability of the central nervous system to coordinate and synchronize the muscles required for the production of speech. This encompasses the laryngeal, vela-pharyngeal, and oral musculature in coordination with the muscles responsible for respiration that must work together in order to produce intelligible speech. Dysarthria can be classified as mild to moderate, wherein the patient slurs at least some words and, at best, can be understood with some difficulty; or severe, wherein the patient's speech is so slurred as to be unintelligible. Cerebral palsy is a cause of dysarthria. One of the speech impairments secondary to cerebral palsy is dyarthric speech. The inability to make articulatory contacts in order to produce bilabial sounds is considered a severe form of dysarthria. Dysarthria is one of the speech impairments treated by the present invention.
The National Institutes of Health (NIH) summary on the status of speech therapy, to improve the speech of children with cerebral palsy states that treatment is currently limited to the enhancement of natural communication forms such as communication symbols and charts or devices that generate synthetic speech and in training communications partners.
Intensive speech and language therapy over the course of several weeks, such as disclosed in Intensive Speech and Language Therapy for Older Children with Cerebral Palsy; a Systems Approach, Pennington et al., Developmental Medicine & Child Neurology; 2010, 52: 337-344, reports at best a 1.14 fold increase to 1.16 fold increase in the number of single or multiple word responses.
Various mechanical and electro-mechanical devices including electrodes are disclosed in the prior art for treating cerebral palsy impaired speech in children. Such devices are disclosed in U.S. Pat. No. 5,213,553, issued May 25, 1993 to Light; and US2006f0161218, published Jul. 20, 2006 to Danilov. Such treatments have had limited improvement in cerebral palsy impaired speech.
The art related to treating a speech impairment secondary to cerebral palsy in children desires a treatment that readily and substantially improves the impairment. The art also desires a treatment as aforesaid wherein the improvement in speech persists without the need for continuous treatment. The present invention accordingly provides a solution.

SUMMARY OF THE INVENTION

This invention, in one principal aspect, is the psychostimulant treatment of a speech and language impairment secondary to cerebral palsy. The invention in another aspect is the psychostimulant treatment of dysarthria in children and adolescents.
This invention in another principal aspect is the evaluation of a subject for the psychostimulant treatment of a speech impairment secondary to cerebral palsy. More specifically, the invention is a method for evaluating a subject for the psychostimulant treatment of a speech impairment secondary to cerebral palsy by diagnosing the subject as having cerebral palsy, determining that the subject has a resultant speech impairment, and then determining that the subject has threshold cognitive capability, and wherein when the subject has cerebral palsy impaired speech and the threshold cognitive capability, the subject is a candidate for psychostimulant treatment to improve the impaired speech. The criteria used to select participants for this invention includes a medical and developmental history and pediatric neurological examination, in addition to a diagnosis of cerebral palsy. The classification of the patient's specific cerebral palsy (e.g. spastic, ataxic, and or dyskinetic) was not particularly a parameter that was considered. The candidates for treatment were required to posses the cognitive abilities equivalent to that of a two year old child. These skills included but were not limited to following two-stage unrelated commands, using a fisted grasp on a pencil to produce vertical strokes on paper and in the non-verbal child, the ability to sequence his limited vocalizations and body movements to a rhythm when modeled (e.g., beat gestures develop at 24-27 months). In addition the participants MRI scans (when available) are assessed to determine (a) a damaged portion, (b) a substantially intact frontal lobe and (c) an undamaged portion extending from the substantially intact frontal lobe to the auditory cortex.
This invention in a more specific aspect is a method for treating cerebral palsy impaired speech in children and adolescents by the administration of a therapeutically effective dose of a psychostimulant to effect a decrease in the difference between chronological age and speech-language equivalent age. In one specific aspect, the present treatment results in the ability to accurately achieve articulatory contacts to produce sounds, and enables the patient to begin producing syllables and words.
The invention is, in one further aspect, a dosage regimen for the treatment of cerebral palsy severe dysarthria by administration of a modest dose of a psychostimulant, with immediate resultant improvement of the impaired speech. The periodic administrations of the psychostimulant over the course of several weeks and/or months, results in a 20-50% improvement the patients ability to produce sounds, syllables and/or words.
Without wishing to be bound by any theory or mechanism, it is believed that the administration of a psychostimulant in a child or adolescent with a speech impairment secondary to cerebral palsy creates alternate neural pathways between the central nervous system and those muscles in the peripheral nervous system responsible for speech production, which neural pathways circumvent the inoperable or damaged portions of the brain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the speech-language age equivalence of Participant 1 before and after treatment pursuant to the present invention;

FIG. 2 shows the percent of correct speech imitations for Participant 1 over the course of the treatment sessions;

FIG. 3 shows the percent of correct responses by Participant 1 in session 6;

FIG. 4 shows the improvement in speech-language age equivalence for Participant 2;

FIG. 5 shows the percent of correct speech imitations by Participant 2;

FIG. 6 shows the improvement in speech-language age equivalence for Participant 3;

FIG. 7 shows the percent correct responses for Participant 3;

FIG. 8 shows the improvement in speech-language age for Participant 4;

FIG. 9 shows the percent of correct speech responses for Participant 4;

FIG. 10 shows the improvement in speech-language age equivalence for Participant 5;

FIG. 11 shows the percent of correct speech imitations for Participant 5;

FIG. 12 shows the percent of correct speech responses for Participant 6 for Sessions 1;

FIG. 13 shows the percent of correct speech responses for Participant 6 for Session 2; and

FIG. 14 shows a summary and comparison of the percent correct speech responses for all the Participants, before and after the treatment sessions.

BACKGROUND OF THE INVENTION

Definitions

The term “subject” as used hereinbefore and hereinafter means a human or other mammal, and includes a patient or participant in a study or clinical trial.
The term “therapeutically effective dose” or “therapeutically effective dosage” as used hereinbefore and hereinafter means an amount of the administered substance that is sufficient to provide an improvement of the speech impairment.
The term “psychostimulant” as used hereinbefore and hereinafter is broadly defined as a drug having antidepressant or mood-elevating properties, and as further discussed hereinafter.
The term “speech impairment secondary to cerebral palsy” is an art cognizable term and further contemplates language impairments.
The term “bilabial consonants” as used hereinbefore and hereinafter means, in the English language, the consonants m/p/b/w and “non-bilabial speech” means the inability to correctly pronounce one of more of the bilabial consonants.
The term “speech-language age equivalence” or “speech-language equivalent age” is the functional speech age of the participant, as determined by a speech language pathologist by methodologies well-known in the speech therapy art.

EXAMPLES

In each of the following examples, the number of correctly pronounced intelligible syllables or words, if any, prior to administration of the psychostimulant is measured against the correctly pronounced intelligible syllables or words after administration of the psychostimulant. Specifically, correctly produced sounds, syllables or words and the use of language prior to the administration of the psychostimulant is used as a baseline to measure against a participant's production after the administration of psychostimulant.

Participant 1

Participant 1 is a 16 year old boy diagnosed with non ambulatory spastic quadriplegic cerebral palsy resulting from hypoxic-ischemic encephalopathy (i.e., lack of oxygen to the brain during birth. An MRI was not available for evaluation. Before the first treatment session (Session 1), Participant 1 could not imitate sounds, was unable to produce modeled sounds in isolation or at the beginning, middle or end of words, was unable to pronounce his own name and had no cognizable sound production. Participant 1, before treatment, had a speech-language age equivalence of a 3 month old child. Age equivalency was determined using the guidelines for vowel and final consonant acquisition. (McLeod S. Child Speech Acquisition). The speech-language age equivalency was measured before the administration and approximately 30 minutes after the administration of the psychostimulant methylphenidate in periodic treatment sessions. Participant 1 was administered methylphenidate 5.0 mg/day approximately three times a week and was evaluated during 6 sessions over a 6 month period (approximately at 1 month intervals). Participant 1 was provided with the art cognizable PROMPT assistance techniques administered by a speech therapist before and after administration of the psychostimulant methylphenidate in treatment Sessions 1-5. The number of correct or intelligible response was measured before and after each treatment session. Participant 1 has a cognitive functional age of a 3½ year old child, as determined by non-verbal techniques well known in the field.
Participant 1, prior to the first administration of methylphenidate in Session 1 correctly imitated 5 words in 52 attempts. After the first administration of the medication, Participant 1 correctly imitated 18 words in 56 attempts. Participant 1, as reported in Table I below, correctly imitated 9.61% of the speech before the initial administration of 5.0 mg methylphenidate, and within about 30 minutes after the initial administration correctly imitated 32.14% of the speech, or an about 3.35 fold improvement in the percentage of correct speech imitations.
FIG. 1 shows the speech-language age equivalence vs. the actual age for Participant 1 over the course of treatment. After six months, Participant 1 had established a speech-language equivalent age of about 25 months. Participant 1 had a phonetic improvement that persisted after the methylphenidate was no longer efficaciously present in the subject and prior to a subsequent administration of methylphenidate.
FIG. 2 shows bar graphs representing the percent of correct word imitations over the course of five treatment sessions. The vertical lines in all bar graphs represent the range of measurements for each set of evaluations. The (Before) bar graphs and averaging slope line for Sessions 1-5 demonstrate a continued persistent improvement.
FIG. 3 shows the percent of correct responses before and after treatment for Participant 1 in Session 6. Session 6 is particularly significant in that Participant 1 was for the first time challenged with polysyllabic words. Participant 1 was afforded no PROMPT assistance before or after administration of the psychostimulant methylphenidate in the polysyllabic word challenge of Session 6. In Session 6, Participant 1 correctly imitated 31.87% of the polysyllabic words prior to administration of the methylphenidate and 50% of the polysyllabic words after administration of the methylphenidate, or an about a 1.57 fold improvement (FIG. 3).
Table I shows the percent of correct speech imitations for Participant 1 and the percent improvement for each session.

TABLE I

Percent of Correct Speech Imitations for Participant 1

TREATMENT
SESSIONS	BEFORE	AFTER	DIFFERENTIAL

Session

1	9.61%	32.14%	22.53
	Session 2	26.83%	33.96%	7.13
	Session 3	30.68%	43.81%	13.13
	Session 4	34.62%	61.9%	27.28
	Session 5	38.98%	57.14%	18.16
	Session 6	31.87%	50.00%	18.13

Participant 2

Participant 2 is a 13 year old girl from a Spanish speaking environment. Participant 2 was diagnosed with spastic hemiplegic cerebral palsy resulting from hypoxic ischemia encephalopathy cerebral palsy. Participant 2 presented with unintelligible speech, consisting of inaudible vowel sounds. An MRI for Participant 2 showed symmetric areas of gliosis and encephalomalacia involving bilateral temporal, frontal and parietal lobes consistent with chronic infarcts in the vascular territories of the middle cerebral arteries. There were smaller focal areas of encephalomalacia and gliosis involving the occipital lobes, right greater than the left. It was determined that Participant 2 had a cognitive capability age of at least about a 2 year old. Prior to treatment, Participant 2 had a speech-language age equivalence of a 3 month old, determined by using guidelines for vowel and consonant acquisition (McLeod S. Children's Speech Acuisition). Participant 2 was treated with 5.0 mg of methylphenidate in three treatment sessions over a period of approximately three months. The participant utilized the medication approximately three times per week to practice with family members. The speech-language age equivalence was measured before and approximately 30 minutes after each administration in the treatment session.
FIG. 4 shows the improvement in speech-language age equivalence for Participant 2 from the date of first treatment wherein prior to the first treatment Participant 2 had a speech-language age equivalence of a three month old, and after three treatment sessions over a three month period, Participant 2 had a speech-language equivalence of a 14 month old.
FIG. 5 shows the percent of correct imitations of speech for three successive treatment sessions. The FIG. 5 linear slope (Before) demonstrates the persistent increasing percentage of correct speech imitations, even before subsequent administrations of the methylphenidate in the treatment session. The vertical lines in all bar graphs represent the range of measurements before and after administration of the psychostimulant.
Referring specifically to FIG. 5 the percentage of correctly pronounced syllables or words was about 10% prior to a first administration of the psychostimulant methylphenidate and more than 30% after a single administration of the psychostimulant methylphenidate, or an increase of about 3.4 fold increase. In Session 1, Participant 2 initially could not pronounce most of the sounds and syllables prior to the administration, but the percentage of correctly pronounced sounds and syllables modeled after Session 2 administration was more than 50%. The percentage of correctly pronounced and intelligible syllables or words, both before and after administration of the psychostimulant methylphenidate generally progressively increased from session 1 through session 3. This demonstrates persistent continued improvement, in contradistinction to transient improvement, in the improvement of the speech impairment. There was persistent improvement, even when the psychostimulant was no longer efficaciously present in the body.
Table II shows the percent of correct speech imitations for Participant 2.

TABLE II

Percent of Correct Speech Imitations for Participant 2

	SESSIONS	BEFORE	AFTER	DIFFERENTIAL

Session

1	10%	34.09%	24.09
	Session 2	21.21%	28.57%	7.36
	Session 3	50.63%	55.77%	5.14

Participant 3

Participant 3 is an 8 year old girl with a Spanish speaking environment in early childhood. Participant 3 was diagnosed with spastic diplegic cerebral palsy due to periventricular leukomalacia resulting from an in utero stroke. An MRI was not available for evaluation. Participant 3, prior to treatment pursuant to the present invention, had the capacity to vocalize one word or at best a two word phrases using present progressive when provided with a visual or pictorial prompt, and had a speech-language equivalent age of a two year old. Participant 3's age equivalence was determined by assessing mean length of utterance and changes in grammatical structure (reference for first years, LS guide to communication milestones). Participant 3 was administered a dose of 5.0 mg/twice per day of methylphenidate, once after breakfast and once after school. Participant 3 was evaluated 2 times at a 6 month interval. After six months, Participant 3 could speak four and five word phrases when provided with a visual or pictorial prompt.
FIG. 6 shows the improvement in speech-language equivalence for Participant 3 over the course of two treatment sessions.
FIG. 7 shows the percent correct multi-word responses for Participant 3 after two treatment sessions. It is important to note that Participant 3 was challenged with more difficult phrases in the second session than in the first session and yet demonstrated improvement. Table III shows the percent of correct speech imitations for Participant 3.

TABLE III

Percent of Correct Speech Imitations for Participant 3

	SESSIONS	BEFORE	AFTER	DIFFERENTIAL

Session

1	66.67%	100%	33.33
	Session 2	77.55%	81.82%	4.27

Participant 4

Participant 4 is an 8 year old girl with an Arabic speaking environment in early childhood. Participant 4 was diagnosed with spastic hemiplegic cerebral palsy resulting from a vascular accident and Protein C deficiency. The MRI for Participant 4 showed a large area of encephalomalacia in the right temporal and posterior frontal lobe with Wallerian degeneration and atrophy involving the right thalamus and right brain stem from the midbrain down to the medulla on the right side. Participant 4, prior to treatment, produced on average two word phrases and predominantly made use of present progressives having a speech-language equivalent age of 24 months. Participant 4's language ability was assessed by determining changes in language ability and average phrase length. Participant 4 was administered 5.0 mg/day of methylphenidate in three treatment sessions spread over the course of 2 months. By the end of 2 months (3 sessions) Participant 4 average response phrase length increased to five words, reflecting a speech-language age equivalence of a 6 year old (72 mos.).
FIG. 8 shows the improvement in speech-language equivalent age for Participant 4.
FIG. 9 shows the percent of correct speech responses for Participant 4. As demonstrated by the linear (Before) averaging slope, there is a persistent increase in the percent of correct responses, even prior to the administration of the psychostimulant in a subsequent treatment session. Table IV shows the percent of correct speech imitations for Participant 4.

TABLE IV

Percent of Correct Speech Imitations for Participant 4

	SESSIONS	BEFORE	AFTER	DIFFERENTIAL

Session

1	63.33%	76%	12.67
	Session 2	76.47%	87.5%	11.03
	Session 3	78.95%	88.14%	9.19

Participant 5

Participant 5 is a five year old girl with a Spanish speaking background. Participant 5 was diagnosed with genetic mutation cerebral palsy resulting in speech impairment. An MRI was not available for evaluation. Participant 5, prior to treatment, had unintelligible speech of about one or two word phrases, accompanied by multiple errors in articulation. Participant 5 had a cognitive ability greater than that of a two year old and language-eqivalency age of 24 months, determined by acquisition of consonant and vowel sounds and mean length of utterances. Prior to treatment, participant 5 was unable to imitate phonemes appropriate for a three-year old. After treatment with 5.0 mg methylphenidate in four monthly treatment sessions, Participant 5 was able to intelligently pronounce some consonants and polysyllabic words and phrases.
FIG. 10 shows the improvement in speech-language equivalence age for Participant 5 over the four monthly treatment sessions. FIG. 11 shows the percent correct speech imitation for Participant 5 over the course of the four treatment sessions. The linear (Before) averaging slope line demonstrates the persistent improvement in the percent of correct speech imitations over the course of treatment sessions, and continued improvement before psychostimulant administration in a subsequent treatment session.
Table V shows the percent correct speech imitations for Participant 5 before and after administration of the methylphenidate over the course of the four treatment sessions.

TABLE V

Percent of Correct Speech Imitations for Participant 5

TREATMENT
SESSIONS	BEFORE	AFTER	DIFFERENTIAL

Session

1	23.68%	47.62%	23.94
	Session 2	23.53%	54.05%	30.53
	Session 3	43.75%	48.98%	5.23
	Session 4	42.34%	59.18%	16.81

Participant 6

Participant 6 is a 16 year old adolescent boy. Participant 6 was diagnosed with Trisomy21 (Down Syndrome) cerebral palsy resulting in speech impairment. An MRI was not available for evaluation. On initial assessment, his speech was stuttered and unintelligible. Participant 6 had the speech-language equivalent age of a 24 month old as determined by types of sounds produced.
In Session 1, after baseline evaluation, a 5.0 mg dose of methylphenidate was administered. Upon re-evaluation, no improvement was noted.
FIG. 12 shows the percent of correct responses for Session 1. A 10 mg dose of the amphetamine Dextroamphetamine was administered in Session 2. Between Sessions 1 and 2, there was a 10 day period in which Participant 6 received 5.0 mg methylphenidate/day. During this 10 day period Participant 6 experienced adverse side effects including loss of appetite and difficulty sleeping. Dextroamphetamine was accordingly administered in Session 2. In Session 2, there was an increase in the speech-language equivalent to a 36 month old. FIG. 13 shows the percent of correct responses by Participant 6 in session 2.
Table VI shows the numerical percent correct responses in Sessions 1 and 2. Table VI demonstrates that in Session 2, Participant 6 showed an about 17% increase in the percent correct responses after the single administration of 10 mg of dextroamphetamine. Participant 6 had an apparent substantial increase in vocabulary access.
It is known in the art that certain non-verbal adolescents have self-promoting gestures to compensate for inadequate vocabulary. Such gestures were measured in Participant 6 before and after Sessions 1 and 2. There was a substantial decline in such gestures after Session 2. This decline experientially correlates with an increased access to and use of vocabulary.

TABLE VI

Percent of Correct Responses for Participant 6

TREATMENT
SESSIONS	BEFORE	AFTER	DIFFERENTIAL

Session

1	63.16%	59.26%	−4.10
	Session 2	69.05%	85.71%	16.66

Summary of Results for all 6 Participants

FIG. 14 shows the percent of correct speech responses for all the Participants prior to the first treatment session and after the final treatment sessions as discussed hereinbefore. FIG. 14 demonstrates that there are increases in the percent of correct speech responses for diverse speech impairments secondary to different types of cerebral palsy in 6 different children and adolescents, Table VII shows the percent of correct speech responses for all Participants.

TABLE VII

Percent of Correct Responses for All Participants

		NUMBER	INITIAL	FINAL
PARTIC-		OF	PRESEN-	ASSESS-	DIFFER-
IPANT	AGE	SESSIONS	TATION	MENT	ENTIAL

Participant

1	16	6	9.61%	50.00%	40.39
Participant 2	13	3	10%	28.57%	18.57
Participant 3	8	2	66.67%	81.82%	15.15
Participant 4	8	3	63.33%	88.14%	24.81
Participant 5	5	4	23.68%	59.18%	35.50
Participant 6	15	2	63.16%	85.71%	22.55

Anecdotal evidence, particularly by the parents or guardians of the Participants, demonstrates that the speech and language improvements, in turn, effected improvements in and retention of socialization skills and emotional well being. The literature suggests that improvements in speech and language functionality correlate with an increase in survival skills and longevity (Katz, R., Life Expectancy for Children with Cerebral Palsy and Mental Retardation: Implications for Life Care Planning).
A repeated T-test was utilized as a statistical analysis of the difference in speech-language ability before and after treatment; a P value of <0.05 was considered significant and with respect to the percent correct responses p=0.0025, and speech-language age equivalence p=0.0309 for all participants.
A broad range of psychostimulants are contemplated by the present invention, and include, but not limited to, by way of example, Adderall® (dextroamphetamine plus amphetamine); atomoxetin (Strattera®); caffeine (Nodoz®, Vivarin®); dextroamphetamine (Dexedrine®); guanfacine (INTUNIV); extended-release tablets: methylphenidate (Concerta°: Metadata®ER: Metadate®CD): pemoline (Cylert®); phentermine (Fastin®, Jonamin®): armodafinil-(NUVIGIL®): benzphetamine (Didrex®): dexmethylphenidate (Foaclin®): diethyipropionate (Tenuate®): lisdexamfetamine dimestylate (Vyvanse®); modafinil (Provigil®); phendimetrizine (Bontril SR®, Prelu-2®); and sibutramine (Meridia®), Quillivant (extended release methylphenidate), Methlyn (immediate release methylphenidate). Methylphenidate®; and Dexedrine® are preferred.
Particularly suitable psychostimulants pursuant to the present invention further include by way of example, methylphenidate and dexmethylphenidiate, as discussed in co-pending application PCT/US2012/038312, filed May 17, 2012, and U.S. Ser. No. 14/112,065, filed Oct. 16, 2013 incorporated herein by reference thereto. Extended release, controlled release and immediate release forms methylphenidate are contemplated as useful psychostimulants. Immediate release methylphenidate is a preferred psychostimulant.
It is also within the contemplation of the present invention to provide a dosage regimen starting with an initial dose of at least about 2.5 mg and increasing the dosage within the same day or in a subsequent day, which increase in dosages would be commensurate with the continuing increase in speech-language age equivalence, particularly where the differential between chronological age and speech-language equivalence age is substantial prior to treatment.
The foregoing demonstrates that modest dosages of 5.0 to 10 mg/day of a psychostimulant result in an increase in the percentage of correctly pronounced intelligible syllables or words. The percentage increase in the correctly produced sounds, syllables, words or language is generally at least about 1.2 fold. The maximum increase is 5 fold in some cases. The foregoing further demonstrates that the increase in correctly pronounced syllables or words persists over time even after the psychostimulant is no longer efficaciously active or present in the body.
In the art related to the treatment of hyperactivity in children, particularly including ADD and ADHD, it is established practice to administer methylphenidate. Psychosocial behavioral disorders such as lack of attentiveness and verbal regression are improved with the administration of methylphenidate, as disclosed in U.S. Pat. No. 6,121,261, issued Sep. 19, 2006 to Glatt et al; and Creager et al., Journal of Speech and Hearing Research, 623-628 (1967). Methylphenidate is administered daily to children suffering psychobehavioral and neuropsychological disorders. The behavioral improvement is short lived, and lasts, at most, several hours after administration of the methylphenidate. Unless such daily dosages are maintained, the subject reverts to his or her attention deficits and hyperactivity.
Intensive speech-language therapy sessions over several weeks, as discussed hereinbefore in paragraph [0009]. reports an improvement of at best about 1.14 fold to 1.16 fold in the number of correctly pronounced single or multiple words, whereas in a single psychostimulant administration pursuant to the present invention, particularly with respect to Participant 1, there was an about 3.34 fold (See FIG. 2, Session 1).
The foregoing demonstrates persistent improvement of the cerebral palsy impaired speech and language, and suggests that alternate neural pathways are being effected. These alternate route neural pathways seemingly persist even when the psychostimulant is no longer efficaciously active or present in the body. This seems to indicate the possibility that alternate pathways have been opened up as a residual effect of the treatment with the medication.
While the invention has been described and illustrated with reference to certain particular embodiments thereof, those skilled in the art will appreciate that various adaptations, changes, modifications, substitutions, deletions, or additions of procedures and protocols may be made without departing from the spirit and scope of the invention. For example, effective dosages other than the particular dosages as set forth herein above may be applicable as a consequence of variations in the responsiveness of the subject being treated for any of the indications with the compounds of the invention indicated above. Likewise, the specific pharmacological responses observed may vary according to and depending upon the particular active compounds selected or whether there are present pharmaceutical carriers, as well as the type of formulation and mode of administration employed, and such expected variations or differences in the results are contemplated in accordance with the objects and practices of the present invention. It is intended, therefore, that the invention be defined by the scope of the claims which follow and that such claims be interpreted as broadly as is reasonable.

Claims

What is claimed is:

1. A method for treating speech impairment secondary to cerebral palsy in a subject in need of such treatment, said method comprises:

(a) providing a psychostimulant;

(b) administering the psychostimulant in a therapeutically effective dose to the subject;

whereby the speech impairment is improved.

2. The method of claim 1, wherein the subject has a chronological age greater than the speech-language age equivalence prior to step (a) and the difference between the chronological age and speech language age equivalence is diminished after step (b).

3. The method of claim 1, wherein there is a diminished difference in chronological age to speech-language age equivalence that persists after the psychostimulant is no longer efficaciously active in the subject.

4. The method of claim 1, wherein the subject is unable to pronounce one or more of the bilabial consonants prior to step (a) and is able to pronounce the one or more bilabial consonants after step (b).

5. The method of claim 1, wherein steps (a) and (b) are repeated periodically over a period of time and wherein the diminishment in the impaired speech continues over the period of time.

6. The method of claim 1, wherein further comprising prior to step (a) determining the cognitive functional age of the subject through non-verbal means, and wherein the cognitive functional age is at least about two years.

7. The method of claim 1, wherein the improved speech impairment comprises a percentage increase in correctly pronounced syllables and words of from at least about 1.2 fold to upwards of 5 fold.

8. The method of claim 1, wherein the subject is a child or adolescent.

9. The method of claim 8, wherein the speech impairment comprises severe dysarthric speech, and the child or adolescent prior to steps (a) and (b), has no or limited bilabial functionality, and after step (b) has improved bilabial functionality.

10. The method of claim 1 comprises a psychostimulant

11. The method of claim 1, wherein the psychostimulant comprises an amphetamine.

12. A method for evaluating a subject for the psychostimulant treatment of a speech impairment secondary to cerebral palsy, said method comprises:

(a) diagnosing the subject as having cerebral palsy;

(b) determining the subject has a speech impairment secondary to the cerebral palsy;

(c) determining the subject has a threshold cognitive capacity; and wherein when the subject has cerebral palsy impaired speechand the threshold cognitive capacity, the subject is a candidate for psychostimulant treatment to diminish the speech impairment.

13. The method of claim 12, step (c) further comprises determining the cognitive age of the subject, and wherein the chronological age is greater than the cognitive age.

14. The method of claim 12, wherein the threshold cognitive capacity is at least about a 2 year old.

15. The method of claim 12, wherein step (b) further comprises measuring the speech-language age equivalence of the subject; and wherein when the chronological age of the subject is greater than the speech-language age equivalence of the subject.

16. The method of claim 12, wherein step (a) further comprises determining that the subject has a substantially intact frontal lobe.

17. The method of claim 16, wherein step (a) further comprises determining that the subject has a damaged portion of the brain, and an undamaged portion extending from the substantially intact frontal lobe to the auditory cortex.

18. The method of claim 12, wherein step (a) further comprises conducting a brain scan and determining that the subject has a substantially intact frontal lobe, a damaged portion, and an undamaged portion extending from the frontal lobe to the auditory cortex.

19. The method of claim 12, wherein step (a) further comprises analyzing a brain scan of the subject.

20. A pharmaceutical intervention for the treatment of speech impairment secondary to cerebral palsy in a subject in need of such said intervention, said pharmaceutical intervention comprises a therapeutically effective dose of a psychostimulant.

21. The pharmaceutical intervention of claim 20, wherein the dose is administered periodically and the treatment persists after the psychostimulant is no longer efficaciously active in the body of the subject and in the absence of or prior to a subsequent dose.

22. The pharmaceutical intervention of claim 20, wherein in the subject is a child or adolescent.

23. A dosage regimen for treating cerebral palsy impaired speech in a subject comprising;

a therapeutically effective dose of a psychostimulant that effects a alternate neural pathway in the brain; and

wherein there is at least about a 20% to several hundred per unit increase in the percent of correctly pronounced intelligible syllables or words after administration of the psychostimulant and an increase in the speech-language age equivalence of the subject.

24. The dosage regimen of claim 23, wherein the subject is a child or adolescent.

25. The dosage regimen of claim 24, wherein the psychostimulant comprises a methylphenidate.

26. The dosage regimen of claim 23, wherein the increase in speech-language persists after the psychostimulant is no longer efficaciously active in the subject.

27. The dosage regimen of claim 26, wherein the psychostimulant comprises an amphetamine.

28. A method for evaluating a subject for psychostimulant treatment of a speech impairment secondary to cerebral palsy, said method comprises:

(a) diagnosing the subject as having a speech impairment secondary to cerebral palsy; and

(b) determining the cognitive functional age of the subject, wherein the cognitive functional age is at least about 2 years, and wherein when the chronological age of the subject is greater than the cognitive functional age of the subject, the subject is determined to be a suitable subject for said treatment.

29. The method of claim 28, wherein step (a) comprises analyzing a brain scan.

30. The method of claim 29, wherein analyzing the brain scan comprises determining (i) a damaged portion, (ii) a substantially intact frontal lobe and (iii) an undamaged portion extending from the substantially intact frontal lobe to the auditory cortex.

31. The method of claim 28, wherein step (b)

comprises: Determining;

(i) in the subject that the subject is following two-step related commands; and

(ii) in a non-verbal subject determining that the subject

is: (A) sequencing limited vocalizations; and

(B) sequencing the vocalizations to the rhythm of the body movements.

32. The method of claim 31, wherein the speech impairment secondary to cerebral palsy comprises dysarthric speech.

33. The method of claim 32, wherein the dysarthric speech comprises non-bilabial speech.

34. A method for treating a subject having a speech impairment secondary to cerebral palsy, said method comprises:

a) diagnosing the subject as having a speech impairment secondary to cerebral palsy;

(b) determining the cognitive functional age of the subject, wherein the cognitive functional age is at least about 2 years, and wherein when the chronological age of the subject is greater than the cognitive functional age, the subject is determined to be a suitable subject for said treatment; and

(c) administering a therapeutically effective dose of a psychostimulant to the suitable subject;

whereby the speech-language age equivalence of the subject is increased.

35. The method of claim 34, wherein step (a) comprises analyzing a brain scan.

36. The method of claim 35, wherein analyzing the brain scan comprises determining (i) a damaged portion, (ii) a substantially intact frontal lobe and (iii) an undamaged portion extending from the substantially intact frontal lobe to the auditory cortex.

37. The method of claim 34, wherein the subject is a child or adolescent.

38. The method of claim 34, wherein step (b)

comprises: Determining;

(i) in the subject that the subject is following two-step related commands; and (ii) in a verbal subject, determining that the subject is using basic two-word combinations; and

(iii) in a non-verbal subject determining that the

subject is: (A) sequencing limited vocalizations; and

(B) moving the body to a rhythm when modeled.