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Central syntropic effects elicited by trigeminal proprioceptive equilibrium in Alzheimer’s disease: a case report
© Vincenzo; licensee BioMed Central Ltd. 2012
Received: 17 October 2011
Accepted: 26 June 2012
Published: 26 June 2012
The presented patient, affected by Alzheimer’s disease, underwent neuropsychological evaluation and functional magnetic resonance imaging investigation under occlusal proprioceptive un-balance and re-balance conditions. Saccadic and pupillometric video-oculographic examinations were performed in order to detect connected trigeminal proprioceptive motor patterns able to interfere with reticular formation cerebellum functions linked to visual and procedural processes prematurely altered in Alzheimer’s disease.
A 66-year-old Caucasian man, affected by Alzheimer’s disease and with a neuropsychological evaluation issued by the Alzheimer’s Evaluation Unit, underwent an electromyographic investigation of the masseter muscles in order to assess their functional balance. The patient showed a bilateral lack of all inferior molars. The extreme myoelectric asymmetry in dental occlusion suggested the rebalancing of masseter muscular functions through concurrent transcutaneous stimulation of the trigeminal nerve supramandibular and submandibular motor branches. The above-mentioned method allows detection of symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch, called orthotic-syntropic bite. A few days later, the patient underwent a new neuropsychological investigation, together with a functional magnetic resonance imaging study, and saccadic, pupillometric video-oculographic examinations in occlusal un-balance and re-balance conditions.
Comparative data analysis has shown that a re-balanced occlusal condition can improve a patient’s cognitive-attentive functions. Moreover, the saccadic and pupillometric video-oculographic investigations have proven useful both in analyzing reticulo-cerebellar subcortical systems, prematurely altered in Alzheimer’s disease, and in implementing neurological evaluations.
An increasing amount of evidence has pointed out the effects generated in aged rats by the loss of molar teeth, with reduction of spatial memory, acetylcholine release from the parietal cortex  and alteration of the septohippocampal cholinergic system , while Yamazaki et al.  have verified that the number of extracted teeth was directly proportional to the loss of spatial memory and to the reduction of trkB messenger ribonucleic acid (mRNA) levels. Furthermore, epidemiological surveys and cross-sectional studies in subjects ranging from 50 to 80 years old have demonstrated that reduced chewing ability or dysfunctional teeth induced senile processes or degeneration of hippocampal neurons, with a decrease of cognitive function and learning effect [4, 5]. On the basis of these findings, studies have been carried out to verify whether the rebalance of myoelectric asymmetries in dental occlusion could modify cognitive-attentive parameters, even in a subject affected by Alzheimer’s disease (AD). In line with the above-mentioned findings, a case report random selection has envisaged only the bilateral lack of all inferior molars and a neuropsychological evaluation of average seriousness. Moreover, computerized saccadic and pupillometric video-oculographic evaluations were performed for their cognitive-attentive and mnemonic nature . These examinations have also allowed for the analysis of the response of reticular formation and cerebellum nuclei connected with visio-motor and procedural processes, prematurely altered in AD [7, 8].
Immediate Rey test
Deferred Rey test
Verbal flux per category
Verbal flux per letter
Immediate visual memory
Instrumental Activities of Daily Living (IADL)
Activities of Daily Living (ADL)
Mini-Mental State Examination (MMSE)
Computerized recordings of pupil diameters
TanGram test, mm
Finally, a neuropsychological report, undertaken after orthotic-syntropic bite application, related the following: ‘The neuropsychological evaluation evidences a higher collaboration of the patient, he is well oriented in space and shows light temporal disorientation. Minor difficulty in the comprehension of simple orders while the impediment to perform more complex tasks remains. The patient has improved short and medium term verbal memory span and his autonomy in performing instrumental activities of daily living, needing assistance only for more complex activities. Ideational slowdown remains. Improvement in executive functions capacities is evidenced, especially in planning, organization and problem solving abilities’, while the MMSE values in re-balance occlusion showed significant improvement (23/30), five points higher than the previous study (18/30) in the habitual condition (Table 1).
The results obtained in occlusal un-balance and re-balance conditions suggest that occlusal proprioceptive asymmetries can elicit central anisotropic effects characterized by minimum order configurations and minimum cortical-subcortical functional differentiations. Even if references to the literature are only indirect at the moment, in this case report the performed tests permit us to deduce that occlusal proprioceptive re-balance in the short/medium term can alter some central functional parameters. Overall, data analysis suggests that consistent effects are seen in the visual-spatial context, in the planning and execution of organization skills, while other functions, such as ideation, reasoning and execution of complex tasks, language and grammar complexity do not display significant results. Improved collaboration on the part of the patient during neuropsychological evaluation and in fMRI execution is a very significant element to take into account. With respect to this, the pupillometric exam can contribute to our understanding of the behavioral change on the part of the patient, because pupillary diameter variation represents an unequivocal evaluative element of the cognitive control state during an evoked task and it is strictly related to locus coeruleus (LC) tonic/phasic activity . In fact, Cohen et al. have demonstrated that during task execution the anterior cingulate, orbitofrontal and prefrontal cortex stimulates LC phasic mode with norepinephrine release. This determines concomitant and immediate pupillary diameter increase, proportional to the released noradrenergic quantity . A pupillometric reduction of −0.21 mm registered in occlusal un-balance during the test (Figures 7 and 8) may be interpreted as the result of cortical strain , while a pupillometric increase of +0.58 mm registered in occlusal re-balance, with a basal pupillometric value of 2.62 mm (Figures 9 and 10), is an index of unquestionable higher coerulean phasic expressivity. This is surprising because the LC is prematurely and deeply interested by AD degenerative processes , and it is also interesting with regard to basal reduction. Trigeminal neurophysiological mechanisms at the core of pupillometric clinical evidence cannot be exhaustively delineated at present, but some relationships among the trigeminal complex, coerulean system and reticular formation can be hypothesized. The literature mainly relates the projections and effects of the LC-norepinephrine system on trigeminal sensorimotor nuclei. Previous studies performed through anterograde and retrograde transport analysis have indicated that many of the regions that received dense inputs from the projected LC neurons, in turn, back upon these coerulei neurons , which are uniformly sensitive to a variety of non-noxious stimuli, including tactile, visual, auditory and taste with specific degree of activation stimulus, [16, 17]. The trigeminal system is strictly connected with the LC and several works have proved that clusters of mesencephalic neuronal branches reach LC-pars compacta, which exhibit a mixture of cellular elements with trigeminal mesencephalic neurons, [15, 18]. Couto et al. demonstrated with retrograde tract tracing using fast blue injections in spinal and principal sensory trigeminal nuclei, the presence of labeled trigeminal mesencephalic and cerulean neurons, . Moreover, Panneton et al. proved trigemino-autonomic connections, using herpes simplex virus 1 (HSV-1) (strain 129), with an anterograde transneuronal transport method that LC and paragigantocellularis nuclei were also labeled . Seemingly, the LC can be activated by increasing the discharge frequency of trigeminal mesencephalic neurons activated both by masseter spindle receptors due to interocclusal excessive space , and by the periodontal for increased occlusal charge, with glutamate release for the activation of presynaptic γ-aminobutyric acid (GABAA) receptors, on the coerulean and peri-coerulean zone . These conditions, characterized by neuromotor facilitation of the mastication preferential side, are inevitably associated with contralateral functional hypoactivity of the trigeminal nerve motor and mesencephalic nuclei. Occlusal motor-proprioceptive activity probably produces a concomitant and homolateral asymmetry of LC/noradrenaline (LC-NE) system phasic modes. Specifically, we may believe that occlusal balance symmetrization can determine, in the trigeminal/LC-NE mesencephalic nucleus pathway, a coerulean activation on the hypoactive occlusal side and a concomitant contralateral reduction which, moreover, could also determine a lower galanin release, normally hyperexpressed in AD, from noradrenergic terminations [23, 24]. In fact, Hoogendijk et al. have demonstrated through the determination of NE and of its 3-methoxy-4-hydroxyphenylglycol (MHPG) metabolite in different brain areas that a significant reverse relationship between the number of coerulean neurons and MHPG/NE ratio both in frontal cortex and in LC can be found in subjects affected by AD, while a significant rise of the MHPG/NE ratio indicates a consistently increased metabolism . In addition to this hypothesis, the coerulean area can also be indirectly activated by the trigeminal motor nucleus. This nucleus does not have a definite nuclear delimitation but it is mixed with lateral reticular formation (LRF) parvocellular neurons , and it is part of the ascending reticular activating system . Presumably, neuromotor hyperactivity of the mastication preferential side elicits a concomitant asymmetric brainstem stimulation reward , including diffused projection catecholaminergic systems of intermediate reticular formation nuclei (IRFn). Previous research has recorded short latency hypsilateral orthodromic responses in LRF and IRFn after electrostimulation of the masseteric nerve and after passive mandible dislocations, . Therefore, a hypothesis can be made that the pupillary diameter increase (3.14 mm) (Figure 10) registered in occlusal re-balance during the evoked task may be the result of a more effective and synchronous phasic expressivity of cerulean neurons, associated with a more suitable reduction (2.62 mm) (Figure 9) of the basal diameter. This last result further validates the functional relationships between coerulean and trigeminal systems because, on the one hand, Rajkowski et al. have demonstrated that basal pupillary diameter is strictly connected to LC tonic discharge frequency. On the other hand, Yabushita et al. have shown that the occlusal vertical dimension increase, which we obtained by orthotic syntropic application, reduces neuromuscular spindle discharge frequency of the masseter muscles . The cited research also suggests that an increased inter-occlusal free space inevitably implies extreme masseter muscle contraction during occlusion in swallowing, determining an increase of spindle and periodontal discharge frequency that hyperactivates the mesencephalic nucleus with glutamate, having depolarizing functions on cerulean neurons. The final result is an increased LC tonic activity that can be detected in the pupillary basal diameter size. The results obtained from saccadic and pupillometric tests confirm the above. Reports in the literature state that saccadic final control is developed by perfect coordination and synchrony of both prepositus hypoglossi and paramedian pontine reticular nuclei [30, 31], and the ipsicerebellar fastigial contralateral to saccadic movement nuclei . Fastigial nuclei can certainly be a target of occlusal asymmetric motor activity, especially of the hypofunctional factor, since the brainstem burst generator cannot produce accurate saccades without oculomotor cerebellum contribution . In fact, these nuclei operate a codification of saccadic command space-time transformation through absolute functional synchrony of the contralateral (initial facilitation of the ‘burst’ scale) and ipsilateral (late ‘burst’ discharge inhibition) fastigial nuclei to saccadic movement and their diminished cooperation can determine saccadic hypo/ipermetry . At present, it is not possible to confirm if the targets of occlusal asymmetry are mainly reticular nuclei, cerebellum fastigial nuclei, or both, but the radical improvement registered in the saccadic test after occlusal re-balance can be interpreted, in apparent contrast with the high stability of the neuronal systems controlling and programming it, as an index of reticulo-cerebellar functional synchrony, equal to what has been hypothesized for coerulean neuron activation modes.
The results of this case report suggest that occlusal un-balance may represent an interferential pattern in some AD central functions. Pupillary dynamic and saccadic motor control examinations can be an efficient investigation tool for implementing neurologic evaluations, and identifying patterns interfering with tonic/phasic LC modes. Within the limits of this case report, further investigations are necessary in order to detect the modalities by which the muscular and periodontal proprioception may modulate the cognitive attentive activity.
Written informed consent was obtained from the patient’s next of kin for publication of this manuscript and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this Journal.
The author sincerely thanks Enrico Cagliari for the acquisition and interpretation of the patient data regarding the fMRI.
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